Neuropeptide Y, NPY receptors, neuroendocrine function,stress, sex differences
Stress is a major causal factor in the etiology of a number of psychiatric-related disorders. However, some individuals remain stress resilient and persevere in the face of intense stress. The mechanisms contributing to stress resistance, or resilience, are beginning to come to light. Numerous studies indicate that NPY is clearly an endogenous anxiolytic (stress reducing or buffering) compound within the amygdala, and its association with resilience in humans has been demonstrated in various studies since the 1980s. Our research is focused on understanding the contribution of neuropeptide systems, such as NPY within the hypothalamus and amygdala, to modulating behavioral and endocrine responses to stress.
The focus of this research is to elucidate the pathways and mechanisms in the brain involved in the generation of stress resilience which will be useful for preventive and therapeutic treatment of anxiety-related disorders. The basolateral nucleus of the amygdala (BLA) is one brain region that is essential for the integration and processing of sensory and memory information into stress responses and emotion. BLA activity is reflective of the balance of inhibitory and excitatory tone which is modulated, in part, by neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF), respectively. In the BLA, NPY not only buffers the actions of CRF, but produces long term stress resilience likely through decreasing the output of the BLA. Recent studies demonstrate that NPY and CRF receptors, present on glutamatergic cells in the BLA, exert opposing physiological actions on their excitability. That both of these peptides are present on these glutamatergic cells makes them a nexus for the two different stress signals in modulating the output of the BLA which contributes to the emotional behaviors of the individual.
Another aspect of our research is to understand the contribution of neuropeptide systems within the hypothalamus (NPY, oxytocin, CRF) to modulating stress responses. Current projects in the laboratory focus on identifying the distribution of NPY receptors within stress responsive areas (such as the paraventricular nucleus of the hypothalamus and central amygdala) and the extent to which these receptors contribute to neuroendocrine function. Along these lines, we have demonstrated sex differences in the neuroendocrine responses to stress and estrogenic regulation of NPY receptor expression and actions in females. The steroid modulation of NPY systems may contribute to the sex differences observed in stress responses.