Behavioural brain research
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Neuropeptide S (NPS) has shown anxiolytic-like effects in rodents after acute administration, but its long-term effects remain unknown. Gene therapy enables the targeted delivery of DNA to cell nuclei, and recombinant adeno-associated viral (rAAV) vectors have been identified as suitable tools for stable overexpression. Thus, to explore the effects of long-term expression of NPS, the present study examined anxiety- and depressive-like effects after rAAV-mediated NPS overexpression in the rat amygdala. ⋯ Immunohistochemical stainings revealed NPS-positive cells in the central and basolateral region of the amygdala in rAAV-NPS but not rAAV-Empty rats, indicating successful transduction. Our study provides novel evidence for sustained anxiolytic-like properties of NPS by transgenic overexpression. These data suggest that rAAV-NPS application deserves further attention as a potential treatment strategy for anxiety in humans.
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Neuroinflammation is often associated with the development of major depressive disorder (MDD)-related symptoms. Previous studies have indicated that activation of glial cells, upregulation of proinflammatory cytokines and dysregulation of adrenergic system in the central nervous system (CNS) could be the key mediators to modulate depression-related behaviors after peripheral immune activation. Central α7 nicotinic acetylcholine receptor (α7 nAChR) has a role in the regulation of the cholinergic anti-inflammatory pathway. ⋯ Following LPS treatment, PNU120596 hindered activation markers of the microglia and astrocytes (cluster of differentiation molecule 11b and glial fibrillary acidic protein) and upregulation of proinflammatory cytokines such as interleukin 1 beta and tumor necrosis factor-alpha in the hippocampus and prefrontal cortex. NE level that was reduced by peripheral LPS challenge was normalized by PNU120596 effects in both brain regions. Overall, the results in this study indicate that activation of α7 nAChR by PAM effectively prevents LPS-induced anxiety, cognitive deficit, and depression-like behaviors and regulates relevant neuroinflammatory markers in the hippocampus and prefrontal cortex.