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婴儿猝死综合征中脑多巴胺能神经元的发育改变:对理解婴儿猝死发病机制的新见解

Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis.

作者信息

Lavezzi Anna Maria

机构信息

"Lino Rossi" Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy.

出版信息

Biomedicines. 2021 Oct 26;9(11):1534. doi: 10.3390/biomedicines9111534.

DOI:10.3390/biomedicines9111534
PMID:34829763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8615170/
Abstract

Sudden infant death syndrome (SIDS) is defined as the unexpected sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation. The SIDS pathogenesis is still unknown; however, abnormalities in brain centers that control breathing and arousal from sleep, including dramatic changes in neurotransmitter levels, have been supposed in these deaths. This is the first study focusing on mesencephalic dopaminergic neurons, so far extensively studied only in animals and human neurological diseases, in SIDS. Dopaminergic structures in midbrain sections of a large series of sudden infant deaths (36 SIDS and 26 controls) were identified using polyclonal rabbit antibodies against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and the dopamine transporter, a membrane protein specifically expressed in dopaminergic cells. Dopamine-immunolabeled neurons were observed concentrated in two specific structures: the pars compacta of the substantia nigra and in the subnucleus medialis of the periaqueductal gray matter. Anatomical and functional degenerations of dopaminergic neurons in these regions were observed in most SIDS cases but never in controls. These results indicate that dopamine depletion, which is already known to be linked especially to Parkinson's disease, is strongly involved even in SIDS pathogenesis.

摘要

婴儿猝死综合征(SIDS)被定义为1岁以下婴儿意外突然死亡,经过全面的病例调查后仍无法解释死因。SIDS的发病机制尚不清楚;然而,这些死亡事件被认为与控制呼吸和从睡眠中唤醒的脑中枢异常有关,包括神经递质水平的显著变化。这是第一项聚焦于中脑多巴胺能神经元的研究,迄今为止,该神经元仅在动物和人类神经系统疾病中得到广泛研究,而在SIDS中尚未有研究。使用针对酪氨酸羟化酶(儿茶酚胺生物合成中的限速酶)和多巴胺转运体(一种在多巴胺能细胞中特异性表达的膜蛋白)的多克隆兔抗体,对大量婴儿猝死(36例SIDS和26例对照)的中脑切片中的多巴胺能结构进行了鉴定。观察到多巴胺免疫标记的神经元集中在两个特定结构中:黑质致密部和导水管周围灰质内侧亚核。在大多数SIDS病例中观察到这些区域多巴胺能神经元的解剖学和功能退化,但在对照中从未观察到。这些结果表明,多巴胺耗竭,已知其尤其与帕金森病有关,甚至在SIDS发病机制中也有密切关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/ac2a6a2bf540/biomedicines-09-01534-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/8c57ba62ba75/biomedicines-09-01534-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/b4a0825c0fff/biomedicines-09-01534-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/ac2a6a2bf540/biomedicines-09-01534-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/8c57ba62ba75/biomedicines-09-01534-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/b4a0825c0fff/biomedicines-09-01534-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/8615170/ac2a6a2bf540/biomedicines-09-01534-g003.jpg

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