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Publication : Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females.

First Author  Luo F Year  2023
Journal  Proc Natl Acad Sci U S A Volume  120
Issue  20 Pages  e2220353120
PubMed ID  37155875 Mgi Jnum  J:342455
Mgi Id  MGI:7548289 Doi  10.1073/pnas.2220353120
Citation  Luo F, et al. (2023) Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females. Proc Natl Acad Sci U S A 120(20):e2220353120
abstractText  Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.
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