Early postnatal alcohol exposure acutely and permanently reduces the number of granule cells and mitral cells in the rat olfactory bulb: a stereological study.
This study demonstrates that exposure to alcohol during a period of rapid brain growth can lead to severe and permanent deficits in the number of granule cells and mitral cells in the main olfactory bulb. Sprague-Dawley rat pups were reared artificially and were administered alcohol over postnatal days (PD) 4 through 9, a period of brain development comparable to part of the human third trimester. The daily alcohol dose of 6.6 g/kg was concentrated into two of the twelve daily feedings, producing high peak blood alcohol concentrations followed by near total clearance. Pups were either sacrificed on PD10 or were allowed to grow to adulthood and sacrificed on PD115. The total number of granule cells and mitral cells in the main olfactory bulb were estimated with the aid of unbiased stereological principles and systematic sampling techniques. Exposure to alcohol resulted in significant reductions in the number of both granule cells and mitral cells on PD10. Significant deficits in both neuronal populations remained on PD115. The results support the hypothesis that alcohol exposure can kill developing neurons and lead to permanent neuronal deficits. Substantial developmental changes also occurred in the total number of mitral cells and granule cells between PD10 and PD115 in the control groups. In untreated rats, the number of granule cells increased from 2.20 x 10(6) on PD10 to 5.06 x 10(6) on PD115, while the number of mitral cells decreased from 5.30 x 10(4) to 4.33 x 10(4) over the same time period. These results demonstrate that there is a natural loss of mitral cells during postnatal development at the same time that granule cell number is increasing.
Bonthius
D J
DJ
Department of Anatomy, University of Otago, Dunedin, New Zealand.
Bonthius
N E
NE
Napper
R M
RM
West
J R
JR
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D006651:Histocytochemistry; D009474:Neurons / Q000187:drug effects; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol