Neuropharmacological study of aged MAM-treated rats

Damage and Repair of Nerve Cell Dna in Toxic Stress*

“…nervous system [65,[68][69][70][71] because the toxin is proposed to selectively target DNA of neuroblasts during development [68,72,73] while sparing postmitotic neurons [68,74] and glial cells [75]. However, the detection of abnormal DNA (presumably alkylated guanine) in the brains of 1-year-old animals [67] treated earlier in life with MAM suggests that mature or postmitotic brain tissue is persistently damaged by the genotoxin.…”

“…Animals exposed in utero to a single dose of MAM develop a progressive decline of learning and memory in the absence of malignancy by 6 months of age [60]. Comparably treated animals also show (1) an age-dependent loss of cortical and hippocampal neurons (A. Rabe, personal communication), (b) significant compromise of dopaminergic and cholinergic function [64,65], (c) a lactate dehydrogenase isozyme pattern characteristic of older animals [66], and (d) abnormal DNA [67]. MAM has been extensively used as a tool by neurobiologists to explore the anatomical and behavioral consequences of perturbing the developing Drug Metabolism Reviews Downloaded from informahealthcare.com by University of California San Francisco on 12/28/14…”