Disruptive neuronal development by acrylamide in the hippocampal dentate hilus after developmental exposure in rats.
To examine whether developmental exposure to acrylamide (AA) impairs neuronal development, pregnant Sprague-Dawley rats were treated with AA at 0, 25, 50 or 100 ppm in drinking water from gestational day 6 until weaning on postnatal day 21. Offspring were immunohistochemically examined at the end of exposure. We investigated the expression of Reelin (a molecule regulating neuronal migration and positioning) in the hilus of the hippocampal dentate gyrus. As a positive control for direct exposure, AA (50 mg/kg body weight) was administered to pups by intraperitoneal injection 3 times per week during the lactation period. As well as pups directly injected with AA, maternally exposed offspring decreased body weight at 100 ppm; increased dose-dependently the number of Reelin-immunoreactive cells (from 25 ppm AA) and glutamic acid decarboxylase 67-immunoreactive cells (from 50 ppm AA), confirming an increase in γ-aminobutyric acid-ergic interneurons. We also noted decreased apoptosis in the neuroblast-producing subgranular zone of the dentate gyrus of maternally exposed pups at 100 ppm, as well as in directly AA-injected pups. These results suggest that a compensatory regulatory mechanism exists to correct impaired neurogenesis and mismigration caused by maternal exposure to AA during neuronal development. The lowest-observed-adverse-effect level of AA was determined to be 25 ppm (3.72 mg/kg body weight/day).
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Bunichiro
B
Ogawa
Takumi
T
Ohishi
Liyun
L
Wang
Miwa
M
Takahashi
Eriko
E
Taniai
Hitomi
H
Hayashi
Kunitoshi
K
Mitsumori
Makoto
M
Shibutani
D020106:Acrylamide / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D020106:Acrylamide; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1