Postnatal methylazoxymethanol: sensitive periods and regional selectivity of effects.
Work on neonatal MAM exposure has focused primarily on exposure within the first week postpartum, and on resulting hypoplasia or stunting of the cerebellum. Rats in this study were exposed to MAM on 4 consecutive postnatal days (PND), beginning at one of six ages, from birth through weaning (PND 1, 5, 9, 13, 17, or 21). MAM was administered subcutaneously in doses of 3, 4, or 5 mg/kg twice per day. Rats were sacrificed at PNDs 28 or 84. The most sensitive age for MAM-induced stunting was determined to be PNDs 1-4. When 5 mg/kg MAM was administered twice daily on PNDs 1-4, body weight was reduced by 24% at age 28 days. Additionally, when compared to control rats, brains of the 28-day-old rats were stunted as follows: whole brain (11%), cerebellum (35%), hippocampus (11%), and olfactory bulb (27%). The effects of PND 1-4 MAM exposure were still evident at 84 days of age when cerebellum and olfactory bulbs from treated rats weighed 30% less than those same regions in control rats. These findings indicate that neonatal exposure to MAM results in permanent stunting in select regions of developing rat brain. This stunting, along with other known MAM effects, can be tailored by exposure age and dose to augment the use of MAM as a positive control for investigation of compounds with neurotoxic potential.
Sullivan-Jones
P
P
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Ali
S F
SF
Gough
B
B
Holson
R R
RR
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol