Turning the ′Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex

Abstract

Recent advancements in technology have enabled researchers to probe the brain with the greater region, cell, and receptor specificity. These developments have allowed for a more thorough understanding of how regulation of the neurophysiology within a region is essential for maintaining healthy brain function. Stress has been shown to alter the prefrontal cortex (PFC) functioning, and evidence links functional impairments in PFC brain activity with neuropsychiatric disorders. Moreover, a growing body of literature highlights the importance of neuropeptides in the PFC to modulate neural signaling and to influence behavior. The converging evidence outlined in this review indicates that neuropeptides in the PFC are specifically impacted by stress, and are found to be dysregulated in numerous stress-related neuropsychiatric disorders including substance use disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia. This review explores how neuropeptides in the PFC function to regulate the neural activity, and how genetic and environmental factors, such as stress, lead to dysregulation in neuropeptide systems, which may ultimately contribute to the pathology of neuropsychiatric diseases.

Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption

“…(G) Binge drinking reduces current-induced spiking in female SST PL neurons (DID: n = 12 cells, control: n = 9 cells, F current (20,380) = 39.339, p < 0.001; F binge (1,19) = 5.754, p = 0.027, F current x binge (20,380) = 0.995, p = 0.467)…”

“…Here we did not assess whether the effects of hM3Dq-induced excitation of PL SST neurons on alcohol binge drinking could be partially attributed to SST peptide release and SST signaling in the PL. The neuropeptide SST has been shown to act largely via a family of Gi/o-coupled receptors (SSTR1-5) to inhibit neuronal excitability (18,19). 0.066, p = 0.798, Fsex x binge(1,39) = 1.704, p = 0.199) (K) Binge drinking did not alter sIPSC frequency in SST cells (control male: n = 11 cells, DID male: n = 10 cells, control female: n = 9 cells, DID female: n = 11 cells; Fsex(1,37) = 0.021, p = 0.884; Fbinge(1,37) = 0.152, p = 0.698, Fsex x binge(1,37) = 3.232, p = 0.080).…”

“…Here we did not assess whether the effects of hM3Dq-induced excitation of PL SST neurons on alcohol binge drinking could be partially attributed to SST peptide release and SST signaling in the PL. The neuropeptide SST has been shown to act largely via a family of Gi/o-coupled receptors (SSTR1-5) to inhibit neuronal excitability (18,19). Future studies should examine the effects of alcohol binge drinking on somatostatin signaling in the PL, and the potential of somatostatin peptide as a therapeutic candidate for excessive alcohol consumption.…”

“…The prelimbic (PL) cortex is a key brain region in addiction and substance abuse (6,7), with projections to many limbic areas (7) including the bed nucleus of the stria terminalis (8,9) and the nucleus accumbens (10) to provide top-down regulation of affective and motivational behaviors. It receives excitatory glutamate afferents from the basolateral amygdala (11,12), and the hippocampus (13), and inhibitory control from a variety of subpopulations of gamma aminobutyric acide (GABA) neurons that express peptidergic markers and receptors such as dynorphin (DYN; 14), corticotropin-releasing factor (CRF; (15,16)), neuropeptide-y (NPY;(17)) and somatostatin (SST; (18,19)). Neurotransmission within the PL is known to be altered in multiple animal models of alcohol exposures, including binge drinking (20) and vapor ethanol exposure (21,22).…”

Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

“…Pharmaceuticals 2021, 14, 643 2 of 13 While several studies have shown that some of the classical neurotransmitters play an important role in cognitive flexibility [12,[19][20][21], the role of neuropeptides in cognitive flexibility is poorly understood. This is surprising, since terminals and receptors of different neuropeptides are (1) localized within the regions of the frontal cortex involved in cognitive flexibility, and (2) down-regulated in neuropsychiatric disorders which are associated with deficits in cognitive flexibility [22]. One exception is probably the neuropeptide orexin, whose levels in the cerebrospinal fluid are upregulated in those schizophrenia patients with fewer negative and disorganized symptoms [23], and for which there is some research regarding its role in cognitive flexibility [24,25].…”