Estrogenic Effect on Hippocampal Theta Rhythm and Memory

Summary

Principal Investigator: C Leranth
Abstract: DESCRIPTION: (Adapted from applicant's abstract): Recent evidence indicates that estrogen treatment in ovariectomized rats enhances performance on memory tasks. Similarly, human observations suggest a beneficial effect of estrogen treatment on cognitive function in Alzheimer's disease. However, those cellular targets of gonadal hormones that are directly involved in memory processes are ill defined. The only solid observations are that systemic hormonal manipulations result in changes in the density of spines and alterations in the intensity of immunostaining for NMDA receptor of hippocampal CAl pyramidal cells. However, hippocampal principal neurons themselves do not, only a small population of interneurons contains nuclear estrogen receptor. On the other hand, neurons in subcortical areas, including the medial septum diagonal band of Broca (MSDB), supramammillary area (SUM), and median raphe (MR) contain nuclear estrogen receptors, and these structures are associated with the generation/regulation of hippocampal theta activity and long term potentiation. Furthermore, hippocampal theta activity, which is greatly influenced by the changing levels of circulating estrogen, in conjunction with long-term potentiation is believed to be involved in memory processes. Therefore, the hypothesis that estrogen, in addition to influencing the hippocampus directly, regulates mnemonic processes by affecting these subcortical areas will be tested by experiments designed to examine the effects of intra-MR, -MSDB, and -SUM administration of estrogen in ovariectomized rats on: 1) changes in dendritic spine density of hippocampal CAl pyramidal cells; 2) mRNA and peptide levels of ionotropic glutamate receptors in the hippocampus; 3) hippocampal theta activity.
Funding Period: 2001-04-06 - 2006-03-31
more information: NIH RePORT

Top Publications

  1. ncbi The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats
    Neil J MacLusky
    Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, New York, New York 10993, USA
    Endocrinology 146:287-93. 2005
  2. pmc Bisphenol A prevents the synaptogenic response to testosterone in the brain of adult male rats
    Csaba Leranth
    Department of Ob Gyn, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, Connecticut 06520, USA
    Endocrinology 149:988-94. 2008
  3. pmc Sex steroids and the dentate gyrus
    Tibor Hajszan
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
    Prog Brain Res 163:399-415. 2007
  4. pmc Extrinsic afferent systems to the dentate gyrus
    Csaba Leranth
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520, USA
    Prog Brain Res 163:63-84. 2007
  5. pmc Effects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats
    Tibor Hajszan
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Endocrinology 148:1963-7. 2007
  6. ncbi Androgen modulation of hippocampal synaptic plasticity
    N J MacLusky
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
    Neuroscience 138:957-65. 2006
  7. ncbi Androgen effects on hippocampal CA1 spine synapse numbers are retained in Tfm male rats with defective androgen receptors
    Neil J MacLusky
    Departments of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Endocrinology 147:2392-8. 2006
  8. pmc The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis
    Neil J MacLusky
    Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, New York, New York 10993 1195, USA
    Environ Health Perspect 113:675-9. 2005
  9. ncbi Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus
    Tibor Hajszan
    Department of Obstetrics, Gynaecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520 8063, USA
    Eur J Neurosci 21:1299-303. 2005
  10. pmc Role of androgens and the androgen receptor in remodeling of spine synapses in limbic brain areas
    Tibor Hajszan
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
    Horm Behav 53:638-46. 2008

Scientific Experts

  • C Leranth
  • Tibor Hajszan
  • Neil J MacLusky
  • N J MacLusky
  • J Prange-Kiel
  • Cynthia L Jordan
  • Jamie A Johansen
  • Victoria N Luine

Detail Information

Publications10

  1. ncbi The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats
    Neil J MacLusky
    Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, New York, New York 10993, USA
    Endocrinology 146:287-93. 2005
    ....
  2. pmc Bisphenol A prevents the synaptogenic response to testosterone in the brain of adult male rats
    Csaba Leranth
    Department of Ob Gyn, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, Connecticut 06520, USA
    Endocrinology 149:988-94. 2008
    ....
  3. pmc Sex steroids and the dentate gyrus
    Tibor Hajszan
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
    Prog Brain Res 163:399-415. 2007
    ....
  4. pmc Extrinsic afferent systems to the dentate gyrus
    Csaba Leranth
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520, USA
    Prog Brain Res 163:63-84. 2007
    ..This strong influence is due to the fact that the majority of the extrinsic afferents terminate on a relatively small, but specific, populations of neurons that are able to control large areas of the hippocampal formation...
  5. pmc Effects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats
    Tibor Hajszan
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Endocrinology 148:1963-7. 2007
    ..However, because this effect of 5alpha-dihydrotestosterone is not completely lost in Tfm rats, additional mechanisms may also be involved...
  6. ncbi Androgen modulation of hippocampal synaptic plasticity
    N J MacLusky
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
    Neuroscience 138:957-65. 2006
    ..The unusual specificity of these responses raises the possibility that effects of androgens on the brain may be mediated via different mechanisms than the masculinizing actions of these steroids in non-neural androgen target organs...
  7. ncbi Androgen effects on hippocampal CA1 spine synapse numbers are retained in Tfm male rats with defective androgen receptors
    Neil J MacLusky
    Departments of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Endocrinology 147:2392-8. 2006
    ..These data are consistent with previous results suggesting that androgen effects on hippocampal spine synapses may involve novel androgen response mechanisms...
  8. pmc The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis
    Neil J MacLusky
    Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, New York, New York 10993 1195, USA
    Environ Health Perspect 113:675-9. 2005
    ..It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines...
  9. ncbi Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus
    Tibor Hajszan
    Department of Obstetrics, Gynaecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520 8063, USA
    Eur J Neurosci 21:1299-303. 2005
    ....
  10. pmc Role of androgens and the androgen receptor in remodeling of spine synapses in limbic brain areas
    Tibor Hajszan
    Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
    Horm Behav 53:638-46. 2008
    ....