Stress Impacts the Regulation Neuropeptides in the Rat Hippocampus and Prefrontal Cortex

Li, Wenxue; Papilloud, Aurélie; Lozano-Montes, Laura; Zhao, Nan; Ye, Xueting; Zhang, Xiaozhe; Sandi, Carmen; Rainer, Gregor

doi:10.1002/pmic.201700408

Cited by 20 publications

(16 citation statements)

References 76 publications

(117 reference statements)

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“…It has been demonstrated that the hippocampal CA1 region contains an abundance of enkephalincontaining neurons and endorphinergic projections [42,43]. Stress can also enhance the release of Metenkephalin in the hippocampus [11,44] to activate µRs or δRs [42]. Stress-induced release of EOPs can efficiently phosphorylate and internalize µRs, δRs or κRs with complicated mechanisms [45][46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval

Shi

Fan²,

Qiao³

et al. 2019

Mol Psychiatry

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Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the µ-opioid receptor (μR), one of the major opioid receptors, strongly influences memory processing in that alterations in μR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether μR signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective μR depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal μR signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal μRs were significantly activated during acute stress. Blockage of hippocampal μRs, non-selective deletion of μRs or selective deletion of μRs on GABAergic neurons (μR GABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a μR GABA-dependent manner. Pharmaceutically enhancing hippocampal GABA A receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate μR GABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval.

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Section: Discussionmentioning

confidence: 99%

Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval

Shi

Fan²,

Qiao³

et al. 2019

Mol Psychiatry

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“…Somatostatin mRNA and peptide in the PFC are reduced following stress in rats (Banasr et al, 2017;Li et al, 2018). Male Sprague-Dawley rats exposed to 36 days of chronic unpredictable stress and 1 day of recovery exhibited significantly decreased SST mRNA measured by quantitative polymerase chain reaction (qPCR) in the PFC when compared to home cage control (Banasr et al, 2017).…”

Section: Stress (Pre-clinical Evidence)mentioning

confidence: 99%

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

Brockway

Crowley

2020

Front. Behav. Neurosci.

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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.

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“…NAc enkephalin levels were also decreased in animals that went through chronic mild stress, and increased by chronic treatment of antidepressants [14]. Additionally, prolonged predator odor and elevated platform stress combined with acute restraint stress downregulated Leu-enkephalin in the hippocampus [15].…”

Section: Introductionmentioning

confidence: 97%

Reduced nucleus accumbens enkephalins underlie vulnerability to social defeat stress

Nam

Chandra

Francis

et al. 2019

Neuropsychopharmacol.

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Enkephalins, endogenous ligands for delta opioid receptors (DORs), are highly enriched in the nucleus accumbens (NAc). They are implicated in depression but their role in the NAc, a critical brain region for motivated behavior, is not fully investigated. To provide insight into enkephalin function we used a chronic social defeat stress paradigm, where animals are either categorized as susceptible or resilient to stress based on their performance in a social interaction test. Compared to controls, susceptible animals showed reduced enkephalin levels in the NAc. Such decrease in enkephalin levels is not due to a change in mRNA of its precursor protein, proenkephalin, in susceptible mice but is consistent with increased mRNA levels of enkephalinases in the NAc of susceptible animals. Systemic administration of enkephalinase inhibitors or NAc infusion of the DOR agonist, SNC80, caused a resilient outcome to CSDS. Both treatments increased phosphorylation of ERK, which was downregulated by social defeat stress. To further validate these results, we also used Q175 knock-in mice, an animal model of Huntington's disease in which enkephalin levels are reduced in striatum and comorbidity with mood disorders is common. Consistent with data in wild-type mice, Q175 animals showed reduced enkephalin levels in the NAc and enhanced susceptibility to a social defeat stress. Overall, our data implicate that depressionlike behavior induced by social defeat stress arises from disrupted DOR signaling resulting from lowered levels of enkephalins, which is partly mediated through elevated expression of enkephalinases.

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Stress Impacts the Regulation Neuropeptides in the Rat Hippocampus and Prefrontal Cortex

Cited by 20 publications

References 76 publications

Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval

Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval

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

Reduced nucleus accumbens enkephalins underlie vulnerability to social defeat stress

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