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Title: Reducing glutamic acid decarboxylase in the dorsal dentate gyrus attenuates juvenile stress induced emotional and cognitive deficits
Author(s): Tripathi, Kuldeep
Demiray, Yunus EmreLook up in the Integrated Authority File of the German National Library
Kliche, Stefanie
Jing, Liang
Hazra, Somoday
Hazra, Joyeeta Dutta
Richter-Levin, Gal
Stork, Oliver
Issue Date: 2021
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-754212
Subjects: PTSD
Dentate gyrus
Stress resilience
Abstract: A high degree of regional, temporal and molecular specificity is evident in the regulation of GABAergic signaling in stress-responsive circuitry, hampering the use of systemic GABAergic modulators for the treatment of stressrelated psychopathology. Here we investigated the effectiveness of local intervention with the GABA synthetic enzymes GAD65 and GAD67 in the dorsal dentate gyrus (dDG) vs ventral DG (vDG) to alleviate anxiety-like behavior and stress-induced symptoms in the rat. We induced shRNA-mediated knock down of either GAD65 or GAD67 with lentiviral vectors microinjected into the dDG or vDG of young adult male rats and examined anxiety behavior, learning and memory performance. Subsequently we tested whether reducing GAD65 expression in the dDG would also confer resilience against juvenile stress-induced behavioral and physiological symptoms in adulthood. While knock down of either isoform in the vDG increased anxiety levels in the open field and the elevated plus maze tests, the knock down of GAD65, but not GAD67, in the dDG conferred a significant reduction in anxiety levels. Strikingly, this manipulation also attenuated juvenile stress evoked anxiety behavior, cognitive and synaptic plasticity impairments. Local GABAergic circuitry in the DG plays an important and highly region-specific role in control of emotional behavior and stress responding. Reduction of GAD65 expression in the dDG appears to provide resilience to juvenile stress-induced emotional and cognitive deficits, opening a new direction towards addressing a significant risk factor for developing stress and trauma-related psychopathologies later in life.
Open Access: Open access publication
Sponsor/Funder: OVGU-Publikationsfonds 2021
Journal Title: Neurobiology of Stress
Publisher: Elsevier
Publisher Place: Amsterdam [u.a.]
Volume: 15
Issue: 2021
Original Publication: 10.1016/j.ynstr.2021.100350
Page Start: 1
Page End: 12
Appears in Collections:Fakultät für Naturwissenschaften (OA)

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