Mihaela Necula

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes
    Miklós Sárvári
    Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony utca 43, Budapest 1083, Hungary
    J Neuroinflammation 9:264. 2012
  2. pmc Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study
    David H Cribbs
    Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, 1226 Gillespie NRF, Irvine, CA 92697, USA
    J Neuroinflammation 9:179. 2012
  3. pmc Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid
    Kathryn E Nichol
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA, USA
    J Neuroinflammation 5:13. 2008
  4. ncbi request reprint The role of caspase cleavage of tau in Alzheimer disease neuropathology
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, Irvine, 92697, USA
    J Neuropathol Exp Neurol 64:104-12. 2005
  5. ncbi request reprint Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
    Neurobiol Aging 23:809-18. 2002
  6. ncbi request reprint Exercise builds brain health: key roles of growth factor cascades and inflammation
    Carl W Cotman
    University of California, Irvine Institute for Brain Aging and Dementia, 1113 Gillespie Building, Irvine, CA 92617 4540, USA
    Trends Neurosci 30:464-72. 2007
  7. ncbi request reprint The brain's microenvironment, early functional loss, and the conversion to Alzheimer's disease
    C W Cotman
    Institute for Brain Aging and Dementia, University of California, Irvine, 1113 Gillespie N R F, Irvine, California 92697 4540, USA
    Ann N Y Acad Sci 924:112-6. 2000
  8. ncbi request reprint Exercise: a behavioral intervention to enhance brain health and plasticity
    Carl W Cotman
    Institute for Brain Aging and Dementia, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697 4540, USA
    Trends Neurosci 25:295-301. 2002
  9. ncbi request reprint Exercise enhances and protects brain function
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, Irvine 92697 4540, USA
    Exerc Sport Sci Rev 30:75-9. 2002
  10. ncbi request reprint The role of neurotrophins in brain aging: a perspective in honor of Regino Perez-Polo
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, 1113 Gillespic NRF, Irvine, CA 92697 4540, USA
    Neurochem Res 30:877-81. 2005

Research Grants

  1. ANIMAL MODEL OF HUMAN AGING AND DEMENTIA
    Carl Cotman; Fiscal Year: 1999
  2. The Canine as an Animal Model of Human Aging
    Carl Cotman; Fiscal Year: 2007
  3. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2007
  4. TRAINING IN THE NEUROBIOLOGY OF AGING
    Carl Cotman; Fiscal Year: 2007
  5. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2005
  6. Gene Expression, Compensation Mechanisms, and Successful Cognitive Aging
    CARL WAYNE COTMAN; Fiscal Year: 2010
  7. BEHAVIORAL AND NEURAL PLASTICITY IN THE AGED
    Carl Cotman; Fiscal Year: 2005
  8. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2004
  9. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2004
  10. ABeta Immunization in Aging
    Carl Cotman; Fiscal Year: 2004

Detail Information

Publications80

  1. pmc Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes
    Miklós Sárvári
    Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony utca 43, Budapest 1083, Hungary
    J Neuroinflammation 9:264. 2012
    ..Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia...
  2. pmc Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study
    David H Cribbs
    Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, 1226 Gillespie NRF, Irvine, CA 92697, USA
    J Neuroinflammation 9:179. 2012
    ..This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer's disease (AD)...
  3. pmc Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid
    Kathryn E Nichol
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA, USA
    J Neuroinflammation 5:13. 2008
    ..Our objective was to determine if exercise could induce a shift from the immune profile in aged (17-19 months) Tg2576 mice to a response that reduces Abeta pathology...
  4. ncbi request reprint The role of caspase cleavage of tau in Alzheimer disease neuropathology
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, Irvine, 92697, USA
    J Neuropathol Exp Neurol 64:104-12. 2005
    ..In addition, a model is presented whereby caspase cleavage of tau provides a mechanistic link between the development of amyloid and tangle pathologies...
  5. ncbi request reprint Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
    Neurobiol Aging 23:809-18. 2002
    ..Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies...
  6. ncbi request reprint Exercise builds brain health: key roles of growth factor cascades and inflammation
    Carl W Cotman
    University of California, Irvine Institute for Brain Aging and Dementia, 1113 Gillespie Building, Irvine, CA 92617 4540, USA
    Trends Neurosci 30:464-72. 2007
    ..Thus, through regulation of growth factors and reduction of peripheral and central risk factors, exercise ensures successful brain function...
  7. ncbi request reprint The brain's microenvironment, early functional loss, and the conversion to Alzheimer's disease
    C W Cotman
    Institute for Brain Aging and Dementia, University of California, Irvine, 1113 Gillespie N R F, Irvine, California 92697 4540, USA
    Ann N Y Acad Sci 924:112-6. 2000
    ..This may be an early mechanism of neurodegeneration, potentially contributing to neuronal vulnerability and disease pathogenesis...
  8. ncbi request reprint Exercise: a behavioral intervention to enhance brain health and plasticity
    Carl W Cotman
    Institute for Brain Aging and Dementia, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697 4540, USA
    Trends Neurosci 25:295-301. 2002
    ..Thus, exercise could provide a simple means to maintain brain function and promote brain plasticity...
  9. ncbi request reprint Exercise enhances and protects brain function
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, Irvine 92697 4540, USA
    Exerc Sport Sci Rev 30:75-9. 2002
    ..Microarray analysis of gene expression provides further support that exercise enhances and supports brain function...
  10. ncbi request reprint The role of neurotrophins in brain aging: a perspective in honor of Regino Perez-Polo
    Carl W Cotman
    Institute for Brain Aging and Dementia, University of California, 1113 Gillespic NRF, Irvine, CA 92697 4540, USA
    Neurochem Res 30:877-81. 2005
    ..We suggest that accumulation of AB and proinflammatory cytokines during aging generates in the brain a "neurotrophin resistance" state that places the brain at risk for cognitive decline and dementia...
  11. ncbi request reprint Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice
    Kathryn Nichol
    Institute for Brain Aging and Dementia, University of California, Irvine, CA, USA
    Alzheimers Dement 5:287-94. 2009
    ..Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that epsilon4 carriers may benefit from regular physical activity...
  12. pmc Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid
    David H Cribbs
    Institute for Brain Aging and Dementia, University of California Irvine, Irvine, CA 92697 4540, USA
    Int Immunol 15:505-14. 2003
    ....
  13. ncbi request reprint Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease
    Paul A Adlard
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
    J Neurosci 25:4217-21. 2005
    ..In support of existing epidemiological studies, this investigation demonstrates that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model...
  14. ncbi request reprint Fas and Fas ligand are associated with neuritic degeneration in the AD brain and participate in beta-amyloid-induced neuronal death
    Joseph H Su
    Institute for Brain Aging and Dementia, 1113 Gillespie Neuroscience Research Facility, University of California Irvine, 92697 4540, USA
    Neurobiol Dis 12:182-93. 2003
    ..These findings suggest that Fas-FasL interactions may contribute to mechanisms of neuronal loss and neuritic degeneration in AD...
  15. pmc Synergistic effects of long-term antioxidant diet and behavioral enrichment on beta-amyloid load and non-amyloidogenic processing in aged canines
    Viorela Pop
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
    J Neurosci 30:9831-9. 2010
    ..Overall, the data indicate that multidomain treatments may be a valuable intervention strategy to reduce neuropathology and improve cognitive function in humans...
  16. ncbi request reprint Accumulation of caspase cleaved amyloid precursor protein represents an early neurodegenerative event in aging and in Alzheimer's disease
    Ming Zhao
    Institute for Brain Aging and Dementia, University of California Irvine, Irvine, CA 92697 4540, USA
    Neurobiol Dis 14:391-403. 2003
    ..These findings raise the possibility that the activation of caspase-3 and cleavage of APP may be involved with neuronal degeneration and that pathways characteristic of apoptosis are activated in AD...
  17. ncbi request reprint Methylene blue inhibits amyloid Abeta oligomerization by promoting fibrillization
    Mihaela Necula
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    Biochemistry 46:8850-60. 2007
    ..If Abeta oligomers represent the primary pathogenic species, then inhibition of this highly toxic species via promotion of formation of less toxic aggregates may be therapeutically useful...
  18. ncbi request reprint The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approaches
    Carl W Cotman
    Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, CA 92697 4540, USA
    J Alzheimers Dis 15:685-707. 2008
    ..In addition, combinatorial treatment approaches can be a powerful strategy for improving brain function through enhancement of multiple molecular pathways...
  19. ncbi request reprint Wheel running following spinal cord injury improves locomotor recovery and stimulates serotonergic fiber growth
    Christie Engesser-Cesar
    Institute for Brain Aging and Dementia, University of California, Irvine, USA
    Eur J Neurosci 25:1931-9. 2007
    ..These observations suggest that improvement in function may be related to changes in serotonin fibers immediately caudal to the injury epicenter...
  20. ncbi request reprint Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
    Science 300:486-9. 2003
    ..These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity...
  21. pmc Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid
    Jiankang Liu
    Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 99:2356-61. 2002
    ..These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function...
  22. pmc Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
    Robert A Rissman
    Institute for Brain Aging and Dementia, University of California, Irvine 92697, USA
    J Clin Invest 114:121-30. 2004
    ..These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline...
  23. pmc Voluntary running attenuates age-related deficits following SCI
    Monica M Siegenthaler
    Reeve Irvine Research Center, Department of Anatomy and Neurobiology, School of Medicine, University of California at Irvine, Irvine, CA 92697 4292, USA
    Exp Neurol 210:207-16. 2008
    ..Importantly, our data indicate that exercise attenuates these age-related deficits following SCI...
  24. pmc Isolated executive impairment and associated frontal neuropathology
    Julene K Johnson
    Department of Neurology and Memory and Aging Center, University of California, San Francisco, Calif, USA
    Dement Geriatr Cogn Disord 17:360-7. 2004
    ....
  25. pmc Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA
    Mol Neurodegener 2:18. 2007
    ..Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils...
  26. pmc Effects of melatonin and age on gene expression in mouse CNS using microarray analysis
    Edward H Sharman
    Center for Occupational and Environmental Health, Department of Community and Environmental Medicine, University of California, Irvine, CA 92697 1825, USA
    Neurochem Int 50:336-44. 2007
    ..This suggests that melatonin treatment may influence the inflammatory responses of old animals, driving them to resemble more closely those occurring in young animals...
  27. pmc Region specific neuron loss in the aged canine hippocampus is reduced by enrichment
    Christina T Siwak-Tapp
    Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
    Neurobiol Aging 29:39-50. 2008
    ..These results suggest that the aged canine hippocampus in the left hemisphere shows selective neuron loss and that behavioral enrichment may reduce this loss...
  28. pmc Short-term supplementation with acetyl-L-carnitine and lipoic acid alters plasma protein carbonyl levels but does not improve cognition in aged beagles
    Lori Ann Christie
    Institute for Brain Aging and Dementia, University of California, Irvine, California 92697 4540, USA
    Exp Gerontol 44:752-9. 2009
    ....
  29. ncbi request reprint Immunization with fibrillar Abeta(1-42) in young and aged canines: Antibody generation and characteristics, and effects on CSF and brain Abeta
    Elizabeth Head
    Institute for Brain Aging and Dementia, Department of Neurology, University of California, 1259 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
    Vaccine 24:2824-34. 2006
    ..A nonsignificant increase in CSF Abeta(1-40) and decrease in Abeta(1-40/1-42) in cortex was detected. Canines may be a useful system for testing an Abeta vaccine...
  30. pmc Differential regulation of inhibitors of apoptosis proteins in Alzheimer's disease brains
    Lori Ann Christie
    Institute for Brain Aging and Dementia, 1113 Gillespie Neuroscience Research Facility, University of California, Irvine, CA 92697, USA
    Neurobiol Dis 26:165-73. 2007
    ..XIAP levels were higher in AD cases and cIAP-2 levels did not vary with clinical status. Our data suggest that decreased NAIP may place neurons at risk for the development of tangles and apoptosis...
  31. pmc Interleukin-1 beta impairs brain derived neurotrophic factor-induced signal transduction
    Liqi Tong
    University of California Irvine, Institute for Brain Aging and Dementia, Irvine, CA 92697 4540, USA
    Neurobiol Aging 29:1380-93. 2008
    ..These results suggest that IL-1 beta places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism...
  32. pmc Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function
    Christina T Siwak-Tapp
    Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697 4540, USA
    Neurobiol Learn Mem 88:249-59. 2007
    ..These results suggest that new neurons in the aged canine dentate gyrus may participate in modulating cognitive functions...
  33. ncbi request reprint Beta-amyloid deposition and neurofibrillary tangle association with caspase activation in Down syndrome
    Elizabeth Head
    Institute for Brain Aging and Dementia, University of California at Irvine, Irvine, CA 92697 4540, USA
    Neurosci Lett 330:99-103. 2002
    ..Abeta within or around neurons in addition to contributing to NFT formation may also trigger apoptotic pathways. Caspase activation may lead to the cleavage of critical cellular proteins and neuronal cell death associated with DS...
  34. ncbi request reprint Hippocampal brain-derived neurotrophic factor gene regulation by exercise and the medial septum
    Nicole C Berchtold
    Institute for Brain Aging and Dementia, University of California, Irvine, California, 92697 4540, USA
    J Neurosci Res 68:511-21. 2002
    ..These results are discussed in relation to their implications for aging and Alzheimer's disease...
  35. pmc Three weeks of running wheel exposure improves cognitive performance in the aged Tg2576 mouse
    Kathryn E Nichol
    Institute for Brain Aging and Dementia, University of California at Irvine, Irvine, CA 92697 4540, USA
    Behav Brain Res 184:124-32. 2007
    ..Our findings demonstrate that exercise can improve cognitive performance in a mouse model of AD even if applied after the development of pathology...
  36. doi request reprint Rhinal and dorsolateral prefrontal cortex lesions produce selective impairments in object and spatial learning and memory in canines
    Lori Ann Christie
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
    J Comp Neurol 511:257-70. 2008
    ....
  37. ncbi request reprint Frontal lobe volume, function, and beta-amyloid pathology in a canine model of aging
    P Dwight Tapp
    Department of Psychology, University of Toronto, Scarborough, Ontario M1C 1A4, Canada
    J Neurosci 24:8205-13. 2004
    ..These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging...
  38. ncbi request reprint Caspase-cleaved amyloid precursor protein and activated caspase-3 are co-localized in the granules of granulovacuolar degeneration in Alzheimer's disease and Down's syndrome brain
    Joseph H Su
    Institute for Brain Aging and Dementia, University of California at Irvine, 92697 4540, USA
    Acta Neuropathol 104:1-6. 2002
    ..A caspase-cleavage product of fodrin that accumulates in many AD and DS neurons is not present in GVD granules. These data support a role for the activation of apoptotic mechanisms in selective compartments exhibiting GVD...
  39. pmc Linear and conformation specific antibodies in aged beagles after prolonged vaccination with aggregated Abeta
    Vitaly Vasilevko
    The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697 4540, USA
    Neurobiol Dis 39:301-10. 2010
    ..Our findings indicate that prolonged immunization results in distinctive temporal changes in antibody profiles, which may be important for other experimental and clinical settings...
  40. ncbi request reprint Exercise-induced gene expression changes in the rat spinal cord
    Victoria M Perreau
    Institute for Brain Aging and Dementia, 1113 Gillespie N R F, University of California Irvine, Irvine, CA 92697, USA
    Gene Expr 12:107-21. 2005
    ..Taken together these data suggest cellular pathways through which exercise may promote recovery in the SCI population...
  41. ncbi request reprint Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury
    Janette Glaser
    Department of Anatomy and Neurobiology, Reeve Irvine Research Center, University of California at Irvine, Irvine, California 92697, USA
    J Neurosci Res 77:701-8. 2004
    ..Improved blood flow and oxygen supply to the injury site may contribute to the functional improvement associated with this treatment...
  42. ncbi request reprint Beta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons
    Liqi Tong
    Institute for Brain Aging and Dementia, University of California Irvine, Irvine, California 92697 4540, USA
    J Neurosci 24:6799-809. 2004
    ..These new findings suggest that Abeta engenders a dysfunctional encoding state in neurons and may initiate and/or contribute to cognitive deficit at an early stage of AD before or along with neuronal degeneration...
  43. ncbi request reprint The timecourse of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise
    Paul A Adlard
    Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
    Neurosci Lett 363:43-8. 2004
    ..Exercise, therefore, was shown to modulate BDNF induction in a time-dependent manner, and this may translate to improvements in neurotrophin-mediated tasks within the CNS...
  44. ncbi request reprint Voluntary wheel running improves recovery from a moderate spinal cord injury
    Christie Engesser-Cesar
    Institute for Brain Aging and Dementia, University of California, Irvine, California 92697 4540, USA
    J Neurotrauma 22:157-71. 2005
    ..05). Finally, fibronectin staining shows no significant difference in lesion size between the two groups. These data represent the first mouse model showing voluntary exercise improves recovery after SCI...
  45. ncbi request reprint Activation of complement pathways after contusion-induced spinal cord injury
    Aileen J Anderson
    Department of Physical Medicine and Rehabilitation, and the Reeve Irvine Center, University of California, Irvine, California 92696 4540, USA
    J Neurotrauma 21:1831-46. 2004
    ..Axonal staining by C1q and Factor B was also observed, suggesting a potential role for the complement cascade in demyelination or axonal degeneration. These data support the hypothesis that complement activation plays a role in SCI...
  46. ncbi request reprint Beta-amyloid deposition and tau phosphorylation in clinically characterized aged cats
    E Head
    Department of Neurology, Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
    Neurobiol Aging 26:749-63. 2005
    ..Thus, the aged cat brain develops AD-related lesions with important morphological and biochemical differences compared to human brain...
  47. ncbi request reprint The exercise-induced expression of BDNF within the hippocampus varies across life-span
    Paul A Adlard
    Institute for Brain Aging and Dementia, University of California, 1125 Gillespie N R F, Irvine, CA 92697 4540, USA
    Neurobiol Aging 26:511-20. 2005
    ..BDNF protein induction may, therefore, not be directly correlated with significant mRNA changes. Exercise may represent a therapeutic tool for disorders which involve a decrease in BDNF...
  48. ncbi request reprint Spatial patterns of mammalian brain aging: distribution of cathepsin D-immunoreactive cell bodies and dystrophic dendrites in aging dogs resembles that in Alzheimer's disease
    Xiaoning Bi
    Department of Psychiatry and Human Behavior, University of California at Irvine, Irvine, California 92697, USA
    J Comp Neurol 464:371-81. 2003
    ..Combined with previous results for rats, these findings indicated that changes in cathepsin D observed in AD, in particular in the temporal lobe, reflect a generalized mammalian pattern of brain aging...
  49. ncbi request reprint Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and down syndrome dementia
    Pinar E Coskun
    Mitochondrial and Molecular Medicine and Genetics, University of California Irvine, Irvine, CA, USA
    J Alzheimers Dis 20:S293-310. 2010
    ..Therefore, mtDNA alterations may be responsible for both age-related dementia and the associated neuropathological changes observed in AD and DSAD...
  50. pmc Gene expression changes in the course of normal brain aging are sexually dimorphic
    Nicole C Berchtold
    Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
    Proc Natl Acad Sci U S A 105:15605-10. 2008
    ....
  51. pmc Methylene blue modulates huntingtin aggregation intermediates and is protective in Huntington's disease models
    Emily Mitchell Sontag
    Department of Biological Chemistry, Psychiatry and Human Behavior, University of California, Irvine, California 92697, USA
    J Neurosci 32:11109-19. 2012
    ..Furthermore, MB treatment also promoted an increase in levels of BDNF RNA and protein in vivo. Thus, MB, which is well tolerated and used in humans, has therapeutic potential for HD...
  52. ncbi request reprint Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct
    Mihaela Necula
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 282:10311-24. 2007
    ..In addition, these data suggest that small molecule inhibitors are useful for clarifying the mechanisms underlying protein aggregation and may represent potential therapeutic agents that target fundamental disease mechanisms...
  53. pmc Axonal mRNA in uninjured and regenerating cortical mammalian axons
    Anne M Taylor
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697 4540, USA
    J Neurosci 29:4697-707. 2009
    ..Our data demonstrate that CNS axons contain many mRNA species of diverse functions, and suggest that, like invertebrate and PNS axons, CNS axons synthesize proteins locally, maintaining a degree of autonomy from the cell body...
  54. pmc Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells
    Munjal M Acharya
    Department of Radiation Oncology, University of California, Irvine, CA 92697 2695, USA
    Proc Natl Acad Sci U S A 106:19150-5. 2009
    ..These results demonstrate the capability to ameliorate radiation-induced normal tissue injury using hESCs, and suggest that such strategies may provide useful interventions for reducing the adverse effects of irradiation on cognition...
  55. ncbi request reprint The induction of the TNFalpha death domain signaling pathway in Alzheimer's disease brain
    Ming Zhao
    Institute for Brain Aging and Dementia, University of California Irvine, Irvine, California, USA
    Neurochem Res 28:307-18. 2003
    ..Our findings suggest that the TNF death receptor pathway and caspases are activated in the early stages of neuronal degeneration in AD...
  56. pmc Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine
    Jiangang Long
    Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
    Neurochem Res 34:755-63. 2009
    ....
  57. ncbi request reprint Patterned cell culture inside microfluidic devices
    Seog Woo Rhee
    Department of Biomedical Engineering, University of California at Irvine, 204 Rockwell Engineering Center, Irvine, CA 92697 2715, USA
    Lab Chip 5:102-7. 2005
    ....
  58. pmc Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: relevance to Alzheimer's disease
    Wycliffe O Opii
    Department of Chemistry, Center of Membrane Sciences, and Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506 0055, United States
    Neurobiol Aging 29:51-70. 2008
    ..These results support the combination treatments as a possible therapeutic approach that could be translated to the aging human population who are at risk for age-related neurodegenerative disorders, including Alzheimer's disease...
  59. ncbi request reprint Long-term treatment with antioxidants and a program of behavioral enrichment reduces age-dependent impairment in discrimination and reversal learning in beagle dogs
    Norton W Milgram
    Division of Life Sciences, University of Toronto, 1265 Military Trail, Scarborough, Ont, Canada M1C 1A4
    Exp Gerontol 39:753-65. 2004
    ..These results suggest that the effectiveness of antioxidants in attenuating age-dependent cognitive decline is dependent on behavioral and environmental experience...
  60. ncbi request reprint Response latency in Canis familiaris: mental ability or mental strategy?
    Pria M D Nippak
    Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
    Behav Neurosci 117:1066-75. 2003
    ..In addition, the slower responding young dogs made fewer errors. Thus, RL appears to reflect the learning strategy applied, rather than the level of mental ability...
  61. ncbi request reprint Exercise increases the vulnerability of rat hippocampal neurons to kainate lesion
    Martin Ramsden
    Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089 0191, USA
    Brain Res 971:239-44. 2003
    ....
  62. ncbi request reprint Visuospatial impairments in aged canines (Canis familiaris): the role of cognitive-behavioral flexibility
    Alan D F Chan
    Institute of Medical Science, University of Toronto, Ontario, Canada
    Behav Neurosci 116:443-54. 2002
    ..Analysis of the response patterns of individual canines indicated that the deficits were related to the use of ineffective strategies and inflexibility in strategy modification...
  63. ncbi request reprint Locomotor activity rhythms in dogs vary with age and cognitive status
    Christina T Siwak
    Institute of Medical Science, University of Toronto, Ontario, Canada
    Behav Neurosci 117:813-24. 2003
    ..The effect of age was less prominent in dogs housed in an indoor/outdoor facility. This suggests that bright sunlight and natural light-dark transitions are better able to consolidate and synchronize the activity rhythms of the dogs...
  64. pmc Interleukin-1beta interferes with signal transduction induced by neurotrophin-3 in cortical neurons
    Rungtip Soiampornkul
    Neuro Behavioral Biology Center, Institute of Science and Technology for Development, Mahidol University, Salaya Campus Nakorn Pathom, Thailand
    Brain Res 1188:189-97. 2008
    ....
  65. ncbi request reprint Chronic antioxidant and mitochondrial cofactor administration improves discrimination learning in aged but not young dogs
    Christina T Siwak
    Institute of Medical Science, University of Toronto, Scarborough, Canada
    Prog Neuropsychopharmacol Biol Psychiatry 29:461-9. 2005
    ..Antioxidants improved the performance of aged dogs on the initial learning tests, suggesting a selective improvement of factors related to the aging process and specific cognitive processes rather than general cognitive enhancement...
  66. ncbi request reprint A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog
    Lori Ann Christie
    Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    Prog Neuropsychopharmacol Biol Psychiatry 29:361-9. 2005
    ....
  67. ncbi request reprint Nutritional management of brain aging in dogs
    Philip Roudebush
    Technical Information Services, Hill s Pet Nutrition Inc, PO Box 148, Topeka, KS 66601, USA
    J Am Vet Med Assoc 227:722-8. 2005
  68. ncbi request reprint Caspase-9 activation and caspase cleavage of tau in the Alzheimer's disease brain
    Troy T Rohn
    Department of Biology, Boise State University, Idaho 83725, USA
    Neurobiol Dis 11:341-54. 2002
    ..Taken together, these results demonstrate the activation of caspases and cleavage of tau in the AD brain, events which may precede and lead to the formation of NFTs...
  69. ncbi request reprint Visuospatial function in the beagle dog: an early marker of cognitive decline in a model of human aging and dementia
    Christa M Studzinski
    Department of Pharmacology, University of Toronto, 1265 Military Trail, Scarborough, Ont, Canada M1C 1A4
    Neurobiol Learn Mem 86:197-204. 2006
    ....
  70. ncbi request reprint Neurobiology of exercise
    Rod K Dishman
    Department of Exercise Science, The University of Georgia, Ramsey Center, 330 River Road, Athens, GA 30602 6554, USA
    Obesity (Silver Spring) 14:345-56. 2006
    ....
  71. ncbi request reprint Musashi1 antigen expression in human fetal germinal matrix development
    Charles Chan
    Brown Medical School, Providence, RI 02903, USA
    Exp Neurol 201:515-8. 2006
    ..Our results indicate that Musashi1 is a useful marker for immature cells in periventricular areas inhabited by stem cells, progenitor cells, and differentiating cells...
  72. ncbi request reprint Achieving and maintaining cognitive vitality with aging
    Howard M Fillit
    Institute for the Study of Aging, Inc, New York, NY 10153, USA
    Mayo Clin Proc 77:681-96. 2002
    ..The data presented in this review should interest physicians who provide preventive care management to middle-aged and older individuals who seek to maintain cognitive vitality with aging...
  73. ncbi request reprint Concept abstraction in the aging dog: development of a protocol using successive discrimination and size concept tasks
    P Dwight Tapp
    Department of Psychology, University of Toronto, 1265 Military Trail, Scarborough, Ont, Canada M1C 1A4
    Behav Brain Res 153:199-210. 2004
    ..Age impairments in concept learning may account for differences in transfer performance on both 3CSC tests...
  74. ncbi request reprint Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels as a central target for the development of human AD and AD-like pathology in aged transgenic mice
    Gjumrakch Aliev
    Microscopy Research Center, Department of Anatomy, Case Western Reserve University and University Hospitals of Cleveland, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Ann N Y Acad Sci 977:45-64. 2002
    ..Our observations demonstrate that vascular wall cells, especially their mitochondria, appear to be a central target for oxidative stress-induced damage...
  75. ncbi request reprint Caspase-cleaved tau accumulation in neurodegenerative diseases associated with tau and alpha-synuclein pathology
    Jodie Newman
    Department of Biology, Boise State University, Boise, Idaho, USA
    Acta Neuropathol 110:135-44. 2005
    ....
  76. pmc Size and reversal learning in the beagle dog as a measure of executive function and inhibitory control in aging
    P Dwight Tapp
    Department of Psychology, University of Toronto, Scarborough, Ontario, Canada M1C 1A4
    Learn Mem 10:64-73. 2003
    ..These separate patterns of reversal impairments in the old and senior dogs may reflect different rates of aging in subregions of the frontal cortex...
  77. ncbi request reprint Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats
    Jiankang Liu
    Department of Molecular and Cell Biology, Uniersity of California, Berkeley, CA 94720, USA
    Ann N Y Acad Sci 1033:117-31. 2004
    ..However, ALC was effective, unlike L-carnitine, in decreasing oxidative damage, including MDA, oxo8dG/oxo8G, and nitrotyrosine, in old rat brain. These data suggest that ALC may be a better dietary supplement than L-carnitine...
  78. ncbi request reprint Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia
    Katherine A Albert
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA
    Arch Gen Psychiatry 59:705-12. 2002
    ..Thus, DARPP-32 occupies a key regulatory position, and may play an important role in the pathophysiological changes in dopamine and glutamate function reported in patients with schizophrenia...
  79. pmc Lipoamide protects retinal pigment epithelial cells from oxidative stress and mitochondrial dysfunction
    Xuesen Li
    Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Free Radic Biol Med 44:1465-74. 2008
    ..These results suggest that LM is a more potent mitochondrial-protective agent and antioxidant than LA in protecting RPE from oxidative damage...
  80. pmc Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid
    Lihong Jia
    Children s Hospital Oakland Research Institute, Oakland, California, USA
    Invest Ophthalmol Vis Sci 48:339-48. 2007
    ....

Research Grants48

  1. ANIMAL MODEL OF HUMAN AGING AND DEMENTIA
    Carl Cotman; Fiscal Year: 1999
    ..Behavioral changes will be correlated with neuropathological findings in hopes of better understanding which component of pathology occurs first and/or contributes the most to age-related cognitive decline. ..
  2. The Canine as an Animal Model of Human Aging
    Carl Cotman; Fiscal Year: 2007
    ....
  3. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2007
    ..Once an initial primary paper is published the overall data will be made available to the field via NACC for various investigators to analyze for the testing their own hypotheses. ..
  4. TRAINING IN THE NEUROBIOLOGY OF AGING
    Carl Cotman; Fiscal Year: 2007
    ....
  5. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2005
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..
  6. Gene Expression, Compensation Mechanisms, and Successful Cognitive Aging
    CARL WAYNE COTMAN; Fiscal Year: 2010
    ..Accordingly, these studies will help provide a rational for including exercise as a formula to promote successful cognitive health during aging. ..
  7. BEHAVIORAL AND NEURAL PLASTICITY IN THE AGED
    Carl Cotman; Fiscal Year: 2005
    ..abstract_text> ..
  8. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2004
    ..Once an initial primary paper is published the overall data will be made available to the field via NACC for various investigators to analyze for the testing their own hypotheses. ..
  9. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2004
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..
  10. ABeta Immunization in Aging
    Carl Cotman; Fiscal Year: 2004
    ..Overall, this project should provide unique insight into the efficacy of immunization with fibrillar Abeta and have direct implications for the design of human clinical trials. ..
  11. ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN
    Carl Cotman; Fiscal Year: 2004
    ..Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. ..
  12. ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN
    Carl Cotman; Fiscal Year: 2003
    ..Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. ..
  13. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2003
    ..Once an initial primary paper is published the overall data will be made available to the field via NACC for various investigators to analyze for the testing their own hypotheses. ..
  14. APOPTOTIC INSULTS SUPPRESS MARKERS NEURONAL PLASTICITY
    Carl Cotman; Fiscal Year: 2004
    ..Together, these experiments may provide support for a mechanism (s) accounting for some of the well-known changes in brain aging and AD, including reduced activity dependent plasticity, synaptic integrity and neuronal survival. ..
  15. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2003
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..
  16. ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN
    Carl Cotman; Fiscal Year: 2003
    ..Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. ..
  17. ABeta Immunization in Aging
    Carl Cotman; Fiscal Year: 2005
    ..Overall, this project should provide unique insight into the efficacy of immunization with fibrillar Abeta and have direct implications for the design of human clinical trials. ..
  18. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2005
    ..Once an initial primary paper is published the overall data will be made available to the field via NACC for various investigators to analyze for the testing their own hypotheses. ..
  19. Gene Expression, Compensation Mechanisms, and Successful Cognitive Aging
    Carl Cotman; Fiscal Year: 2009
    ..Accordingly, these studies will help provide a rational for including exercise as a formula to promote successful cognitive health during aging. ..
  20. Brain Aging & Gene Expression Patterns Using Microarrays
    Carl Cotman; Fiscal Year: 2006
    ..Once an initial primary paper is published the overall data will be made available to the field via NACC for various investigators to analyze for the testing their own hypotheses. ..
  21. APOPTOTIC INSULTS SUPPRESS MARKERS NEURONAL PLASTICITY
    Carl Cotman; Fiscal Year: 2003
    ..Together, these experiments may provide support for a mechanism (s) accounting for some of the well-known changes in brain aging and AD, including reduced activity dependent plasticity, synaptic integrity and neuronal survival. ..
  22. ABeta Immunization in Aging
    Carl Cotman; Fiscal Year: 2003
    ..Overall, this project should provide unique insight into the efficacy of immunization with fibrillar Abeta and have direct implications for the design of human clinical trials. ..
  23. ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN
    Carl Cotman; Fiscal Year: 2000
    ..Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. ..
  24. MECHANISMS OF PATHOLOGICAL NEURITIC & SOMAL DEGENERATION
    Carl Cotman; Fiscal Year: 2000
    ..The studies proposed in this application will provide new and basic biological findings potentially relevant to a wide array of normal and pathological events involving synaptic remodeling and neurite degeneration. ..
  25. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2000
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..
  26. APOPTOTIC INSULTS SUPPRESS MARKERS NEURONAL PLASTICITY
    Carl Cotman; Fiscal Year: 2001
    ..Together, these experiments may provide support for a mechanism (s) accounting for some of the well-known changes in brain aging and AD, including reduced activity dependent plasticity, synaptic integrity and neuronal survival. ..
  27. The Canine as an Animal Model of Human Aging
    Carl Cotman; Fiscal Year: 2002
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..
  28. MECHANISMS OF PATHOLOGICAL NEURITIC & SOMAL DEGENERATION
    Carl Cotman; Fiscal Year: 2002
    ..The studies proposed in this application will provide new and basic biological findings potentially relevant to a wide array of normal and pathological events involving synaptic remodeling and neurite degeneration. ..
  29. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2002
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..
  30. ABeta Immunization in Aging
    Carl Cotman; Fiscal Year: 2002
    ..Overall, this project should provide unique insight into the efficacy of immunization with fibrillar Abeta and have direct implications for the design of human clinical trials. ..
  31. ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN
    Carl Cotman; Fiscal Year: 2002
    ..Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. ..
  32. APOPTOTIC INSULTS SUPPRESS MARKERS NEURONAL PLASTICITY
    Carl Cotman; Fiscal Year: 2002
    ..Together, these experiments may provide support for a mechanism (s) accounting for some of the well-known changes in brain aging and AD, including reduced activity dependent plasticity, synaptic integrity and neuronal survival. ..
  33. ABeta Immunization in Aging
    Carl Cotman; Fiscal Year: 2001
    ..Overall, this project should provide unique insight into the efficacy of immunization with fibrillar Abeta and have direct implications for the design of human clinical trials. ..
  34. MECHANISMS OF PATHOLOGICAL NEURITIC & SOMAL DEGENERATION
    Carl Cotman; Fiscal Year: 2001
    ..The studies proposed in this application will provide new and basic biological findings potentially relevant to a wide array of normal and pathological events involving synaptic remodeling and neurite degeneration. ..
  35. ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN
    Carl Cotman; Fiscal Year: 2001
    ..Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. ..
  36. CANINE AS AN ANIMAL MODEL OF HUMAN AGING
    Carl Cotman; Fiscal Year: 2001
    ..Overall, this project should provide unique insight into the role of oxidative damage and subsequent molecular cascades on the progression of brain aging and cognitive decline. ..