Wednesday, November 28, 2018

Study with rats sheds light on why women are roughly twice as likely as men to develop depression, anxiety and other stress-related problems, including difficulty with attention

Early Life Stress Drives Sex-Selective Impairment in Reversal Learning by Affecting Parvalbumin Interneurons in Orbitofrontal Cortex of Mice. Haley L. Goodwill et al. Cell Reports, Volume 25, ISSUE 9, P2299-2307.e4, Nov 27 2018.

    •    Early life stress leads to select deficits in reversal learning in female mice
    •    Impaired rule-reversal learning is associated with decreased PV and GAD67 in OFC
    •    Optogenetic silencing of OFC PV+ cells recapitulates ELS effects on reversal learning
    •    Optogenetic silencing of mPFC PV+ cells impairs rule shifting, but not reversal learning

Summary: Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of females remain unknown. Here, ELS is associated with impaired rule-reversal (RR) learning in females, but not males. Impaired performance was associated with decreased expression and density of interneurons expressing parvalbumin (PV+) in orbitofrontal cortex (OFC), but not other interneuron subtypes. Optogenetic silencing of PV+ interneuron activity in OFC of control mice phenocopied RR learning deficits observed in ELS females. Localization of reversal learning deficits to PV+ interneurons in OFC was confirmed by optogenetic studies in which neurons in medial prefrontal cortex (mPFC) were silenced and associated with select deficits in rule-shift learning. Sex-, cell-, and region-specific effects show altered PV+ interneuron development can be a driver of sex differences in cognitive dysfunction.

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