Tajuddin Nuzhath F, Orrico Luisa A, Eriksen Jason L, Druse Mary J
Division of Molecular & Cellular Biochemistry, Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.
Alcohol. 2003 Apr;29(3):157-64. doi: 10.1016/s0741-8329(03)00024-7.
Previously, results of studies from our laboratory have shown that the offspring of ethanol-fed female rats have a significant decrease in serotonin (5-HT) neurons and glia that contain S100B, an essential trophic factor for the development of 5-HT neurons. The deficiency of S100B-immunopositive glia was detected during the vulnerable period in 5-HT neuron development and in brain areas proximal to these neurons. The reductions of both 5-HT neurons and S100B-positive glia were prevented by maternal treatment with a 5-HT(1A) agonist (i.e., ipsapirone or buspirone). In the current study, we investigated whether the offspring of ethanol-fed rats had a general decrease in the density of glial cells in the brain areas that contain 5-HT neurons, and we determined whether these changes were prevented by maternal treatment with ipsapirone between gestational days (GDs) 13 and 20. We estimated the density of vimentin-positive glia of the midline raphe glial structure (MRGS) at GD 20 and postnatal day (PND) 5 and of glial fibrillary acidic protein (GFAP)-positive astrocytes proximal to the dorsal and median raphe at PNDs 5 and 19. The results of this study provide evidence that in utero ethanol exposure is associated with a reduced density of GFAP-immunopositive astrocytes proximal to the dorsal and median raphe. Maternal ipsapirone treatment significantly increased astroglial density in the dorsal raphe at PNDs 5 and 19 and in the median raphe at PND 5, such that it either prevented (dorsal raphe, PNDs 5 and 19) or blunted (median raphe, PND 5) the effects of ethanol.
此前,我们实验室的研究结果表明,用乙醇喂养的雌性大鼠的后代中,血清素(5-羟色胺,5-HT)神经元以及含有S100B(5-HT神经元发育所必需的营养因子)的神经胶质细胞显著减少。在5-HT神经元发育的易损期以及这些神经元附近的脑区中,检测到了S100B免疫阳性神经胶质细胞的缺乏。母体用5-HT(1A)激动剂(即伊沙匹隆或丁螺环酮)进行治疗可防止5-HT神经元和S100B阳性神经胶质细胞的减少。在本研究中,我们调查了用乙醇喂养的大鼠的后代在含有5-HT神经元的脑区中神经胶质细胞密度是否普遍降低,并且我们确定了在妊娠第13天至第20天期间母体用伊沙匹隆治疗是否能防止这些变化。我们估计了妊娠第20天和出生后第5天(PND 5)中线中缝神经胶质结构(MRGS)中波形蛋白阳性神经胶质细胞的密度,以及出生后第5天和第19天(PND 19)背侧和中缝附近的胶质纤维酸性蛋白(GFAP)阳性星形胶质细胞的密度。本研究结果提供了证据,表明子宫内乙醇暴露与背侧和中缝附近GFAP免疫阳性星形胶质细胞密度降低有关。母体用伊沙匹隆治疗显著增加了出生后第5天和第19天背侧中缝以及出生后第5天中缝处的星形胶质细胞密度,从而要么防止了(背侧中缝,出生后第5天和第19天)要么减弱了(中缝,出生后第5天)乙醇的影响。