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- Title
Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors.
- Authors
Steullet, Pascal; Cabungcal, Jan-Harry; Kulak, Anita; Kraftsik, Rudolf; Ying Chen; Dalton, Timothy P.; Cuenod, Michel; Do, Kim Q.
- Abstract
Elevated oxidative stress and alteration in antioxidant systems, including glutathione (GSH) decrease, are observed in schizophrenia. Genetic and functional data indicate that impaired GSH synthesis represents a susceptibility factor for the disorder. Here, we show that a genetically compromised GSH synthesis affects the morphological and functional integrity of hippocampal parvalbumin-immunoreactive (PV-IR) interneurons, known to be affected in schizophrenia. A GSH deficit causes a selective decrease of PV-IR interneurons in CA3 and dendate gyrus (DG) of the ventral but not dorsal hippocampus and a concomitant reduction of β/γ oscillations. Impairment of PV-IR interneurons emerges at the end of adolescence/early adulthood as oxidative stress increases or cumulates selectively in CA3 andDGof the ventral hippocampus. Such redox dysregulation alters stress and emotion-related behaviors but leaves spatial abilities intact, indicating functional disruption of the ventral but not dorsal hippocampus. Thus, a GSH deficit affects PV-IR interneuron's integrity and neuronal synchrony in a region- and time-specific manner, leading to behavioral phenotypes related to psychiatric disorders.
- Subjects
OXIDATION-reduction reaction; GENOTYPE-environment interaction; GLUTATHIONE; ANTIOXIDANTS; MENTAL illness
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 7, p2547
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3857-09.2010