title: Redox dysregulation affects the ventral but not dorsal hippocampus: impairment of parvalbumin neurons, gamma oscillations, and related behaviors.
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 beta/gamma oscillations. Impairment of PV-IR interneurons emerges at the end of adolescence/early adulthood as oxidative stress increases or cumulates selectively in CA3 and DG of 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.
authors.affiliation: Department of Psychiatry, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1008 Prilly-Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Steullet
authors.forename: Jan-Harry
authors.initials: JH
authors.lastname: Cabungcal
authors.forename: Anita
authors.initials: A
authors.lastname: Kulak
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kraftsik
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Dalton
authors.forename: Michel
authors.initials: M
authors.lastname: Cuenod
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Do
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000221:Adaptation, Ocular / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D064032:Calbindin 2; D064026:Calbindins; D003214:Conditioning, Classical; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear; D005247:Feeding Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000172:deficiency; D005978:Glutathione / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology*; D007395:Interneurons / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism*; D010364:Pattern Recognition, Visual / Q000502:physiology; D012201:Reward; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D064032:Calbindin 2; D064026:Calbindins; D018690:Excitatory Amino Acid Agonists; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D000080242:8-Hydroxy-2'-Deoxyguanosine; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D003849:Deoxyguanosine; D005978:Glutathione; D007608:Kainic Acid