Transitory glutathione deficit during brain development induces cognitive impairment in juvenile and adult rats: relevance to schizophrenia.
Glutathione (GSH) metabolism dysfunction is one risk factor in schizophrenia. A transitory brain GSH deficit was induced in Wistar (WIS) and mutant (ODS; lacking ascorbic acid synthesis) rats using BSO (l-buthionine-(S,R)-sulfoximine) from post-natal days 5-16. When GSH was re-established to physiological levels, juvenile BSO-ODS rats were impaired in the water maze task. Long after treatment cessation, adult BSO-WIS/-ODS rats showed impaired place discrimination in the homing board with distributed visual or olfactory cues. Their accuracy was restored when a single cue marked the trained position. Similarly, more working memory errors were made by adult BSO-WIS in the radial maze when several olfactory cues were present. These results reveal that BSO rats did not suffer simple sensory impairment. They were selectively impaired in spatial memory when the task required the integration of multimodal or olfactory cues. These results, in part, resemble some of the reported olfactory discrimination and cognitive impairment in schizophrenia.
Cabungcal
Jan-Harry
JH
Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland. Jan-Harry.Cabungcal@hospvd.ch
Preissmann
Delphine
D
Delseth
Caroline
C
Cuénod
Michel
M
Do
Kim Q
KQ
Schenk
Françoise
F
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000096:biosynthesis; D001921:Brain / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003463:Cues; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000172:deficiency* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D000857:Olfaction Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009949:Orientation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012559:Schizophrenia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D012727:Sex Characteristics; D012903:Smell / Q000502:physiology
D005978:Glutathione; D001205:Ascorbic Acid