Prenatal ethanol exposure affects the activity and mRNA expression of neuronal membrane enzymes in rat offspring.
In order to elucidate molecular mechanisms underlying brain dysfunction in offspring exposed to ethanol in utero, subclinical doses of ethanol that do not have apparent structural effect on the offspring were administered intraperitoneally to pregnant rats at various gestational stages. We measured the activity of membrane marker enzymes and the level of mRNA of myelin proteins of the offspring brain. The activity of a myelin specific enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased in ethanol-exposed offspring. This effect was not related to the period of gestation or the dose of ethanol. Perikaryonal enzymes, acetylcholinesterase and Na+, K(+)-ATPase, were significantly affected in groups exposed to ethanol at early fetal stage and in high doses. Expression of mRNAs of CNP and myelin basic proteins decreased significantly in the ethanol-treated group, with abnormal developmental profile suggesting a relationship with delayed myelination in offspring exposed to ethanol in utero. The present findings suggest that in spite of the low doses of ethanol that do not cause clinical symptoms in the offspring, prenatal exposure to ethanol affects the level of mRNA of membrane enzyme proteins in the offspring brain, consequently causing a corresponding reduction in enzyme activity, that may lead to neuronal dysfunction. In a separate study, blood ethanol levels were found to reach a maximum level within 30 min after injection and be undetectable after 5 to 10 h. No accumulation effects due to daily injection were observed.
Kojima
H
H
Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.
Mineta-Kitajima
R
R
Saitoh-Harada
N
N
Kurihara
T
T
Takahashi
Y
Y
Furudate
S
S
Shirataka
M
M
Nakamura
K
K
Tamai
Y
Y
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000648:ultrastructure*; D002462:Cell Membrane / Q000201:enzymology*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D007700:Kinetics; D004676:Myelin Basic Protein / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015430:Weight Gain
D004676:Myelin Basic Protein; D012333:RNA, Messenger; D000431:Ethanol; D000110:Acetylcholinesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000254:Sodium-Potassium-Exchanging ATPase