Helen Scharfman

New York University, USA

Abstract

[O12] The dual role of neuropeptide co-transmitters: regulation of synaptic transmission and neurogenesis

Helen E. Scharfman¹ and William P. Gray²; ¹The Nathan Kline Institute, Orangeburg, NY, USA, New York University Langone Medical Center, New York, NY, USA, ²University of Southampton, Southampton, United Kingdom

A large literature now exists which demonstrates that neuropeptides exert robust effects on synaptic transmission and neuronal excitability. More recently, it has been shown that neuropeptides also influence postnatal neurogenesis in the dentate gyrus, one of two brain areas where neurogenesis persists after birth. Actions of neuropeptides on dentate gyrus neurogenesis raise the possibility that there are more ways for neuropeptides to influence hippocampal function than previously considered.  Furthermore, there are new ways for neuropeptidergic manipulations to be relevant to disease, because dentate gyrus neurogenesis is implicated in depression, Alzheimer’s disease, schizophrenia, and epilepsy.

One example is neuropeptide Y (NPY), which is colocalized with GABA in a subset of interneurons in the dentate gyrus.  Release of NPY is known to depress synaptic transmission in hippocampus, primarily by Y2 or Y5 receptors. The other subtype of NPY receptor that is expressed in hippocampus, Y1, appears to mediate actions of NPY to stimulate proliferation of new neurons. Therefore, a system appears to have evolved to allow NPY to exert different functions, under separate receptor-mediated control. 

Another example is brain-derived neurotrophic factor (BDNF), which is a member of the neurotrophin family. One of the pathways where BDNF protein is highly expressed is the pathway from dentate gyrus to area CA3, the mossy fibers. In the mossy fiber pathway, which is essential to hippocampal function, BDNF enhances synaptic transmission and synaptic plasticity.  BDNF also stimulates proliferation of neuronal precursors in the dentate gyrus. It appears that BDNF exerts these functions primarily by binding to a single receptor, TrkB.  Therefore, BDNF may act in multiple ways to stimulate neuronal and synaptic plasticity, without as much separation - at the receptor level - as NPY.  However, different signal transduction arms of TrkB could still provide independent pathways of regulation. . 

Therefore, it may be possible to use pharmacological manipulations of neuropeptides to regulate synaptic transmission without affecting proliferation, and vice-versa. This selective tools could be useful clinically, in disorders where the dentate gyrus, NPY, and BDNF are already implicated, such as depression, Alzheimer’s disease, schizophrenia and epilepsy.

Keywords: neuropeptide Y (NPY), brain derived neurotrophic factor (BDNF), dentate gyrus, hippocampus

Biography

Helen E. Scharfman, Ph.D. is Professor of Child & Adolescent Psychiatry at New York University Langone Medical Center and Research Scientist VII at The Nathan S. Kline Institute for Psychiatric Research.

Dr. Scharfman graduated from Vassar College, completed doctoral training in Pharmacology at the Uniformed Services University of the Health Sciences, and postdoctoral study in Neurological Surgery at the University of Washington.  She was then a Research Associate in the Department of Neurobiology and Behavior at the State University of Stony Brook before joining the Departments of Pharmacology and Neurology at Columbia University and starting her own laboratory at Helen Hayes Hospital.  In 2000, she became Director of the Center for Neural Recovery and Rehabilitation Research at Helen Hayes Hospital and received the New York State Department of Health Employee of the Year award in 2005.  The following year she moved her laboratory to The Nathan Kline Institute, a part of the Office of Mental Health in New York State, and changed primary academic affiliation to New York University. She remains an adjunct member of the faculty at Columbia University.

Dr. Scharfman’s research has focused on synaptic plasticity since graduate school, where she focused on long-term potentiation and GABAergic modulation of visual cortical neurons in brain slices. As a postdoctoral fellow, she began to characterize the neurons located in the dentate gyrus hilus, which are vulnerable in several diseases, such as temporal lobe epilepsy. After several years working in the field of epilepsy research, the laboratory expanded to include neuroendocrinology, neurogenesis, and neurotrophin research not only as they apply to epilepsy, but also psychiatric illness and learning disorders.