Disruption of the Glutamate–Glutamine Cycle Involving Astrocytes in an Animal Model of Depression for Males and Females

作者: Virginie Rappeneau , Amanda Blaker , Jeff R. Petro , Bryan K. Yamamoto , Akiko Shimamoto

DOI: 10.3389/FNBEH.2016.00231

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摘要: Background: Women are twice as likely men to develop major depression (MD). The brain mechanisms underlying this sex disparity not clear. Disruption of the glutamate-glutamine cycle has been implicated in psychiatric disturbances. This study identifies sex-based impairments involving astrocytes using an animal model depression. Methods: Male and female adult Long-Evans rats were exposed chronic social defeat stress (CSDS) for 21 days, a modified resident-intruder paradigm. Territorial aggression was used males maternal females induce depressive-like deficits intruders. phenotype assessed with intake saccharin solution, weight gain, estrous cycle, corticosterone (CORT). Behaviors displayed by intruders during daily encounters residents characterized. Rats handling controls each sex. Ten days after last encounter, both subjected no-net-flux vivo microdialysis assess glutamate accumulation extracellular glutamine nucleus accumbens (NAc). contralateral hemispheres determining changes astrocytic markers, including glial fibrillary acidic protein (GFAP) transporter-1 (GLT-1). Results: Both male reduced over course CSDS, compared their pre-stress period respective controls. exhibited submissive/defensive behaviors territorial receiving sideways threats bites. These showed reductions striatal GLT-1 spontaneous NAc, Female isolated aggression, immobility, rearing, self-grooming. Their non-reproductive extended. Also, they prefrontal accumbal GFAP+ cells GLT-1, When 10 µM infused, these significant Infusions Conclusions: Twenty-one or produced impaired PFC-striatal network may be linked more than males.

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