Anthony N van den Pol

..A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin...

..Intratumoral injection of tumors with VSV-12'GFP dramatically suppressed tumor growth and enhanced survival. Together these data suggest this recombinant virus merits further study for its oncolytic and vaccine potential...

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..Together, these data support the view that MCH neurons may integrate information within the arousal system in favor of energy conservation...

..DG-VSVs with genes coding for different color reporters allow multicolor visualization of neurons wherever applied...

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..This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).]..

..These results suggest that coupling IFN administration with current treatments may reduce CMV infections in the developing brain...

..These data suggest that brain injury enhances CMV invasion of the brain, but only when the adaptive immune system is compromised, and that the brain's ability to resist viral infection recovers rapidly after injury...

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..Cytomegaloviruses thus have potential as useful vectors for gene transfer and labeling central nervous system cells, with the actions of CMV being dependent on a number of factors...

..Thus a number of factors related to spike-dependent stabilization of neuronal connections, including Hebbian mechanisms, that are generally applied to glutamate transmission may also participate in stabilization of GABA circuits...

..Together, these data suggest a relative affinity of rVSV for some neuronal types in the CNS, adding to our understanding of the long-lasting changes in rodent behavior found after transient VSV infection...

..Together these data suggest that the hypothalamus, via hypocretin projections, may therefore be in a position to enhance arousal and modulate plasticity in higher brain centres through the developing LC...

..Virus infections of the brain can lead to transient or permanent neurologic or psychiatric dysfunction. Some of the complexities in establishing the causal role of viruses in brain disease are explored here...

..A short intercell distance may increase the concentration of limited amounts of trophic factors available to a nearby cell, and once contact is made, a neuronal membrane provides a superior substrate for neuritic elongation...

..Astrocytes in the same cultures showed no immunolabeling. These results indicate that GABA is present very early in the development of hypothalamic neurons and is in a position to be released...

..Together, these data suggest that tonically active inhibitory mGluRs are expressed on local hypocretin-sensitive glutamate neurons within the lateral hypothalamus that modulate the output of the hypocretin arousal system...

..The greater potency of hcrts in direct excitation compared with indirect inhibition suggests a negative feedback function for the latter at higher levels of hcrt activity...

..Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA...

..POMC cells may hypothetically serve as a conditional relay station downstream of kisspeptin and GnIH to signal the availability of energy resources relevant to reproduction...

..These data raise the possibility that the time dissociation described by cannabinoid users may result in part from altered circadian clock function and/or entrainment to environmental time cues...

..Together, these results show a depolarizing response to extracellular ATP that would lead to an increased activity of the hypocretin arousal system...

..Norepinephrine and serotonin, transmitters of other arousal systems, decreased spike frequency and evoked outward currents, whereas acetylcholine and histamine had little effect...

..Thus Hcrt effects within the septum should increase hippocampal acetylcholine release and thereby promote hippocampal arousal...

..Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors...

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..These data suggest that catecholamines evoke strong inhibitory actions on hypocretin neurons and suggest negative feedback from catecholamine cells that may be excited by hypocretin...

..Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells...

..Together, these results show that the family of neuropeptide Y modulators reduces the activity of inhibitory GABA neurons in the ARC by multiple presynaptic and postsynaptic mechanisms...

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..Dual PYY(3-36) inhibition of both NPY and POMC cells may temporarily reduce the contribution of arcuate cells to feeding circuits, enhancing the role of other CNS loci...

..Together, these results show that cannabinoids have opposite effects on MCH and hypocretin neurons. These opposing actions could help explain the increase in feeding and reduction in arousal induced by cannabinoids...

..This in turn could suppress gonadotropin release, influence reproductive development and alter sex behaviour...

..Depolarizing actions of GABA and GABA-dependent burst-firing may synchronize a rapid release of GABA, NPY, and SST, leading to pre- and postsynaptic inhibition of excitatory hippocampal circuits...

..Together, our data suggest that TRH inhibits MCH neurons by increasing synaptic inhibition from local GABA neurons. Inhibition of MCH neurons may contribute to the TRH-mediated reduction in food intake and sleep...

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..We concluded that some, but not all, attenuated VSV mutants display a favorable oncolytic profile and merit further investigation...

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..Thus, in contrast to previous suggestions that hypocretin inhibited POMC cells, our results demonstrate robust direct excitation of POMC neurons by hypocretin...

..These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells...

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..These results suggest that hypocretin neurons may be able to exercise a high degree of modulatory control over postsynaptic targets using multiple neuropeptides with target-dependent actions...

..Together, these results indicate that nicotine has a number of similar actions, but also a few different actions, on POMC and NPY neurons that could contribute to the weight loss associated with smoking...

..Quantitative PCR analysis of how VSVrp30a selectively infected tumor cells suggested multiple mechanisms, including cell surface binding and internalization...

..Together, these data are consistent with the view that the hypocretin system may be an important direct target for drugs of abuse, including opiates, that induce sedation and mental lethargy...

..The attenuation of calcium currents is consistent with an inhibitory action for the peptide in neurons...

..Together, our results demonstrate that activation of the interferon pathway protects normal human brain cells from VSV infection while maintaining the vulnerability of human glioblastoma cells to viral destruction...

..Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia in vivo but showed a modest infection of developing neurons...

..Systemic adoptive transfer may be a rapid and effective approach to preventing CMV entrance into the brain and for reducing neurotropic infection...

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..These results indicate that attenuated recombinant viruses show reduced neurovirulence and that peripheral immunization blocks the lethal actions of all VSVs tested...

..Together, these data suggest that four (VSV, Sindbis virus, MVMi, and MVMp) of the nine viruses studied merit further analysis for potential therapeutic actions on glioblastoma...

..Similar methods may be useful in the development of physiologically sensitive fluorescent reporter proteins and directed evolution or mutagenesis of proteins in general...

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..Overall, we find that the potential efficacy of VSV as an oncolytic agent extends to nonhematologic mesodermal tumors and that unusually strong resistance to VSV oncolysis can be overcome with interferon attenuators...

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..This system appears to play a key role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature...

..Signaling via the MAPK cascade and the transcription factor CREB appear to play a substantial role in this process...

..Similar to other neurons of the arcuate nucleus that serve multiple homeostatic functions, the function of the excitatory arcuate glutamate neuron may include other roles in addition to that of energy homeostasis. ..

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..The primary goal of these studies is to test the efficacy and safety of variant oncolytic VSVs as the first step as a potential treatment for currently incurable human brain tumors. ..

..Understanding the role of the endogenous opioid in hypocretin cells should also facilitate the understanding and treatment of narcolepsy. ..

..GABA's excitatory actions during development are widespread throughout the brain. Thus, what we learn from our experiments on hypothalamic neurons should have general applicability to other CNS neurons. ..

..These experiments will help us understand the mechanisms associated with CMV-induced neurological dysfunction, and how to combat the virus within the brain with minimal complications. ..

..Together, these experiments will provide a better understanding of the cellular mechanisms underlying hypocretin actions and neuronal communication to and from hypocretin neurons. ..

..These experiments will help us understand the mechanisms associated with CMV-induced neurological dysfunction, and how to combat the virus within the brain with minimal complications. ..

..Studies of the cellular physiology of MCH neurons should provide a better understanding of the role of this system in regulating energy homeostasis and obesity. ..

..The primary goal of these studies is to test the efficacy and safety of variant oncolytic VSVs as the first step as a potential treatment for currently incurable human brain tumors. ..

..Understanding the role of the endogenous opioid in hypocretin cells should also facilitate the understanding and treatment of narcolepsy. ..

..These experiments will help us understand the mechanisms associated with CMV-induced neurological dysfunction, and how to combat the virus within the brain with minimal complications. ..

..Virus mediated changes in intracellular ion levels, ion currents, transmitter responses, and membrane properties will be compared in CMV infected and control cells. ..

..We will use their transgenic mouse to study the attributes of olfactory ensheathing cells in enhancing axonal recovery after cord injury. ..

..NPY is potentially of great interest because its primary action in the normal hippocampus appears to be one of depressing hyperexcited neurons, without a substantial effect on normal neurotransmission. ..

..Thus, what we learn from our experiments on hypothalamic neurons should have general applicability to other CNS neurons. ..