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Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Effects of chronic manganese exposure on working memory in non-human primates
J S Schneider1, E Decamp, K Clark
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, 521 JAH, Philadelphia, PA 19107, USA. jay.schneider@jefferson.edu
Abstract:
Human exposure to manganese (Mn) has been associated with a variety of cognitive deficits including learning and memory deficits. However, results from epidemiological studies have been inconsistent in describing the nature of such cognitive deficits. The present study was conducted to evaluate the effects of chronic Mn exposure on memory functioning in non-human primates and to correlate behavioral outcome with brain Mn levels in an attempt to explain outcome variability seen in prior studies. Cynomolgus macaque monkeys were trained to perform memory-related tasks (spatial working memory, non-spatial working memory, reference memory) and exposed to manganese sulfate (15-20 mg/kg/week) over an exposure period lasting 227.5+/-17.3 days. Blood manganese levels were in the upper range of levels reported for human environmental, medical or occupational exposures. By the end of the manganese exposure period, animals developed mild deficits in spatial working memory, more significant deficits in non-spatial working memory and no deficits in reference memory. Linear regression analyses showed that for most brain regions sampled, there was a significant inverse relationship between working memory task performance and brain Mn concentration. These results suggest that chronic exposure to levels of manganese achieved in this study may have detrimental effects on working memory and that Mn levels achieved in several brain regions are inversely related to working memory performance.
Insights
Chronic manganese (Mn) exposure in primates impaired working memory, with higher brain Mn levels correlating to worse performance. These findings help explain inconsistencies in human studies on manganese and cognitive deficits.
Area of Science:
- Neuroscience
- Toxicology
- Primate Research
Background:
- Human manganese (Mn) exposure is linked to cognitive deficits, but epidemiological findings are inconsistent.
- Understanding the specific nature of Mn-induced cognitive deficits and their relationship to brain Mn levels is crucial.
Purpose of the Study:
- To investigate the effects of chronic manganese sulfate exposure on memory functions in non-human primates.
- To correlate behavioral outcomes with brain manganese concentrations to explain variability in human studies.
Main Methods:
- Cynomolgus macaque monkeys were trained on spatial working memory, non-spatial working memory, and reference memory tasks.
- Monkeys received chronic manganese sulfate exposure (15-20 mg/kg/week) for approximately 227.5 days.
- Blood and brain Mn levels were measured, and performance on memory tasks was analyzed in relation to Mn concentrations.
Main Results:
- Manganese exposure led to mild spatial working memory deficits and more significant non-spatial working memory deficits.
- No deficits were observed in reference memory performance.
- A significant inverse relationship was found between working memory performance and Mn concentration in most brain regions.
Conclusions:
- Chronic exposure to manganese at levels comparable to human environmental, medical, or occupational exposures can detrimentally affect working memory.
- Brain manganese levels are inversely correlated with working memory performance, offering an explanation for outcome variability in human studies.
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