title: Chronic manganese exposure impairs visuospatial associative learning in non-human primates.
abstract: Manganese (Mn) is an essential trace metal nutrient, however, excess Mn can be neurotoxic. The degree to which chronic environmental or occupational exposures to Mn in adults cause neuropsychological dysfunction is of considerable interest. Descriptions of neuropsychological dysfunction following chronic Mn exposure have been somewhat inconsistent though, likely owing to different measures of exposure in different populations, complicated by factors of mixed exposures and differences in neuropsychological tests administered. We previously described up-regulation of the mRNA expression for amyloid-beta (A-beta) precursor-like protein 1 (APLP1) and the presence of A-beta diffuse plaques in frontal cortex of Mn-exposed monkeys. The present study examined Mn-induced changes in performance on a paired associate learning (PAL) task that has been suggested as a marker for preclinical Alzheimer's disease. Aspects of performance of this task were affected early following initiation of Mn exposure. Thus, PAL performance may be a sensitive and valuable tool for the early, preclinical detection of incipient dementia and it may also be a sensitive tool for detecting cognitive dysfunction from Mn exposure. The current cognitive data, combined with our previous findings, suggest that frontal cortex may be a particularly sensitive target for the effects of Mn on cognition and that chronic Mn exposure may initiate or accelerate a process that could lead to or predispose to Alzheimer's like pathology and cognitive dysfunction.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address: jay.schneider@jefferson.edu.
authors.forename: J S
authors.initials: JS
authors.lastname: Schneider
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States.
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States.
authors.forename: M
authors.initials: M
authors.lastname: Ault
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, United States.
authors.forename: T R
authors.initials: TR
authors.lastname: Guilarte
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal; D003071:Cognition / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D008345:Manganese / Q000009:adverse effects*; D020149:Manganese Poisoning / Q000150:complications / Q000473:pathology*; D010153:Paired-Associate Learning / Q000187:drug effects*; D011323:Primates
chemical_list: D008345:Manganese
keywords: Cognition; Manganese; Monkeys