Stem cell therapy: social recognition recovery in a FASD model.

Stem cell therapy: social recognition recovery in a FASD model.
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DOI:
10.1038/tp.2012.111
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发表时间:
2012-11-13
影响因子:
6.8
通讯作者:
Saito T
Saito T
中科院分区:
医学1区
文献类型:
--
作者:
Shirasaka T;Hashimoto E;Ukai W;Yoshinaga T;Ishii T;Tateno M;Saito T

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为了更好地了解胎儿酒精谱系障碍(FASD)的细胞发病机制和干细胞治疗的益处,我们将孕鼠暴露于乙醇中,然后将神经干细胞(NSCs)与去端肽胶原复合物静脉注射给新生大鼠,研究前扣带皮层、海马和杏仁核中GABA能中间神经元数量和突触蛋白密度的恢复。产前乙醇暴露减少小白蛋白阳性表型的GABA能中间神经元和突触后密度蛋白95在这些领域的水平。静脉注射NSC治疗逆转了这些减少。此外,用NSC治疗逆转了受损的记忆/认知功能和社会互动行为。这些实验强调了突触重塑和GABA能中间神经元发生在FASD的病理生理学和治疗中的重要作用,并强调了静脉内NSC给药在FASD中利用去端肽胶原的治疗潜力。
To better understand the cellular pathogenetic mechanisms of fetal alcohol spectrum disorder (FASD) and the therapeutic benefit of stem cell treatment, we exposed pregnant rats to ethanol followed by intravenous administration of neural stem cells (NSCs) complexed with atelocollagen to the new born rats and studied recovery of GABAergic interneuron numbers and synaptic protein density in the anterior cingulate cortex, hippocampus and amygdala. Prenatal ethanol exposure reduced both parvalbumin-positive phenotype of GABAergic interneurons and postsynaptic density protein 95 levels in these areas. Intravenous NSC treatment reversed these reductions. Furthermore, treatment with NSCs reversed impaired memory/cognitive function and social interaction behavior. These experiments underscore an important role for synaptic remodeling and GABAergic interneuron genesis in the pathophysiology and treatment of FASD and highlight the therapeutic potential for intravenous NSC administration in FASD utilizing atelocollagen.
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