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PMID: 20164340 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Redox dysregulation affects the ventral but not dorsal hippocampus: impairment of parvalbumin neurons, gamma oscillations, and related behaviors.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 30 ·No. 7 ·2010-02-17 ·Pages 2547-58

Steullet P, Cabungcal JH, Kulak A, Kraftsik R, Chen Y, Dalton TP, Cuenod M, Do KQ

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.

MeSH Terms
8-Hydroxy-2'-Deoxyguanosine Adaptation, Ocular/physiology Analysis of Variance Animals Animals, Newborn Behavior, Animal/physiology Biological Clocks/drug effects,physiology Calbindin 2 Calbindins Conditioning, Classical Deoxyguanosine/analogs & derivatives,metabolism Electric Stimulation/methods Electroencephalography/methods Excitatory Amino Acid Agonists/pharmacology Exploratory Behavior/physiology Fear Feeding Behavior/physiology Gene Expression Regulation/genetics Gene Expression Regulation, Developmental/drug effects Glutamate-Cysteine Ligase/deficiency Glutathione/deficiency Hippocampus/cytology Interneurons/metabolism Kainic Acid/pharmacology Male Maze Learning/physiology Mice Mice, Inbred C57BL Mice, Knockout Neural Pathways/physiology Oxidation-Reduction Oxidative Stress/physiology Parvalbumins/metabolism Pattern Recognition, Visual/physiology Reward S100 Calcium Binding Protein G/metabolism Spatial Behavior/physiology
Chemicals
Calbindin 2 Calbindins Excitatory Amino Acid Agonists Parvalbumins S100 Calcium Binding Protein G 8-Hydroxy-2'-Deoxyguanosine GCLM protein, human Glutamate-Cysteine Ligase Deoxyguanosine Glutathione Kainic Acid
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Steullet Pascal
Department of Psychiatry, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1008 Prilly-Lausanne, Switzerland.
Cabungcal Jan-Harry
Kulak Anita
Kraftsik Rudolf
Chen Ying
Dalton Timothy P
Cuenod Michel
Do Kim Q
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3857-09.2010
Published
2010-02-17
Pages
2547-58
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6634545
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.3857-09.2010 PMC Full Text View journal details
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