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Brain and Nerve No to Shinkei Volume 33, Issue 12 （December 1981）

Brain and Nerve 脳と神経 33巻12号（1981年12月発行）

Japanese English

原著

ラット胎児性アルコール症候群における2´，3´—cyclic nucleotide 3´—phosphohydrolaseの発達 ACTIVITY OF 2´, 3´-CYCLIC NUCLEOTIDE, 3´-PHOSPHOHYDROLASE IN THE CENTRAL NERVOUS SYSTEM OF RAT FETAL ALCOHOL SYNDROME DURING DEVELOPMENT 鈴木伸幸 ¹ , 田中晴美 ¹ , 有馬正高 ¹ Nobuyuki Suzuki ¹ , Harumi Tanaka ¹ , Masataka Arima ¹ ¹国立武蔵療養所神経センター・疾病研究第2部 ¹Division of Child Neurology, National Center for Nervous, Mental and Muscular Disorders pp.1207-1212

発行日 1981年12月1日 Published Date 1981/12/1

DOI https://doi.org/10.11477/mf.1406204860

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Abstract 文献概要
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はじめに

　胎児性アルコール症候群（fetalalcohol syndrome，以下FAS）はアルコール飲用が女性にも普及してきていること，精薄の大きな原因となることなどからわが国でもしだいに注目されてきている。欧米に比しわが国での報告は未だ少なく，高島ら^13）の一家族例の報告，田中ら^14）の自験例6例を含む全国調査結果の報告がある。動物モデルを作成してそのメカニズムの研究も進められており，田中ら^15）はラットモデルを作成し，エタノール濃度，飲用期間，飲用時期の違いによる胎仔の死亡率，体量などにつき報告している。われわれはFASにみられる精神運動発達遅延に着目し，脳の生化学的発達の面からその遅れ，回復の有無などを追求してきた。前回われわれはラットモデルを作成し，胎生期および出生後の大脳，肝のRNA,DNA，蛋白について報告した^12）。今回は前回と同様の実験モデルを作成し，中枢神経系各部位の2´，3´—cyclic nucleotide 3´—phosphohydrolase（CNPase）を測定することにより胎生期に投与されたエタノールが出生後の脳の発達，特にミエリン形成にどのように影響を与えるかを検討した。

Mental retardation is the most serious symptom of fetal alcohol syndrome (FAS) in human. Retarded myelinogenesis of the central nervous system was shown histologically and biochemically in the ex-perimental rats. 2´, 3´-cyclic nucleotide 3´-phospho-hydrolase (CNPase) is a maker enzyme of myelin and its activity has been reported to correlate with the score of learning test in some experimental rats such as hypothyroidism. In order to obtain some insight into the chemical myelinogenesis and mental retardation in FAS, CNPase activity was measured for the various parts of the brain and spinal cord in the experimental rats.

Female Wistar rats of experimental group (group E) were provided 30% ethanol and solid diets ad lib for 100 days before mating and during the period of gestation. Control group (group C) was given water and solid diets ad lib in the same period. The offsprings were decapitated in 5-day-interval from 5th to 60th day after birth. Offsprings were weighed and brain and spinal cord were rapidly removed. Brain was separated into cerebral gray matter, cerebral white matter, brain stem, olfactory bulb and cerebellum. CNPase actvity was measured by the method of Prohaska et al.

Development of CNPase activity (U/mg protein) was different in respective regions. On 5th day after birth all regions except for cerebral gray matter had activity in C group. The activities in cerebral gray matter and olfactory bulb were lower than other regions but continued to increase on 60th day. The activity in cerebral white matter showed twice as high as that in gray matter and still increased gradually on 60th day. The activity in cerebellum was low and did not increase after 30th day. The activities in brain stem and spinal cord were high and no increase was observed after 30th day. The activity in E group was lower than that of C group during 5 to 15th day after birth in 6 regions especially white matter and brain stem which had higher activity than others in C group. After 20th day no difference was observed in all regions of both group. No difference was observed in both groups regard to protein (per gram wet weight) development in the 6 regions.

In summary, if the activity of CNPase reflects myelination, only the early stage of myelination is disturbed in the rat model of FAS. As mye-linogenesis in rat occurs after birth, so ethanol given during gestational period has prolonged effect after birth with regard to myelination. Since mye-linogenesis in human being occurs during intra-uterine life, human FAS will receive longer and more adverse effects of ethanol than rat model.