title: Age-related vulnerability to diencephalic amnesia produced by thiamine deficiency: the role of time of insult.
abstract: Age is a risk factor for the development of many neurological disorders, including alcohol-related neurological disorders. A rodent model of Wernicke-Korsakoff Syndrome (WKS), acute pyrithiamine-induced thiamine deficiency (PTD), produces diencephalic damage and impairments of memory similar to what is seen in WKS patients. Advanced age increases the vulnerability to the cascade of acute and some chronic neurological events caused by PTD treatment. Interactions between PTD treatment and age at the time of treatment (3, 10, or 21 months), in addition to the effects of an increased recovery period, were examined relative to spatial memory impairment and neuropathology in Fischer 344 rats. Although acute neurological disturbances and medial thalamic brain lesions were more prevalent in middle-aged and senescent rats exposed to PTD treatment, relative to young rats, behavioral data did not support the view that PTD and aging have synergistic effects. In addition, both advanced age and PTD treatment result in a loss of basal forebrain cholinergic neurons, though there was no interaction. Despite the fact that no convincing evidence was found for an effect of extended recovery time on neuropathology measures, young rats given an extensive recovery period displayed less working memory impairment. In summary, these data provide evidence for an increased susceptibility of the aged rat to the acute neurological consequences and diencephalic pathology associated with PTD treatment and indicated a similar vulnerability of the middle-aged rat. However, the synergistic interaction between aging and PTD treatment in thalamic tissue loss did not express behaviorally.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY 13905, USA.
authors.forename: Shane R
authors.initials: SR
authors.lastname: Pitkin
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Savage
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000647:Amnesia / Q000209:etiology*; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D002452:Cell Count; D002552:Cerebral Ventricles / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004032:Diet; D004193:Discrimination Learning; D004195:Disease Models, Animal; D007150:Immunohistochemistry / Q000379:methods; D020915:Korsakoff Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011745:Pyrithiamine / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013037:Spatial Behavior; D013831:Thiamine / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D000963:Antimetabolites; D011745:Pyrithiamine; D002795:Choline O-Acetyltransferase; D013831:Thiamine