Defining the Vulnerability Window of Anesthesia-Induced Neuroapoptosis in Developing Dentate Gyrus Granule Cells — A Transgenic Approach Utilizing POMC-EGFP Mice

Autor: Yi-Heng Liu, Zhi-Ru Wang, Kai Wei, Yu Zhang, Ping Chen, Andreas W. Loepke, Feng-Yan Shen, Ying-Wei Wang, Meng Deng
Rok vydání: 2019
Předmět:
Zdroj: Neuroscience. 415:59-69
ISSN: 0306-4522
DOI: 10.1016/j.neuroscience.2019.07.009
Popis: Exposure to commonly used anesthetics is associated with widespread neuroapoptosis in neonatal animals. Vulnerability of developing hippocampal dentate gyrus granule cells to anesthetic neurotoxicity peaks approximately 2 weeks after cell birth, as measured by bromodeoxyuridine birth dating, regardless of the age of the animal. The present study examined whether the vulnerable window can be further characterized by utilizing a transgenic approach. Proopiomelanocortin enhanced green fluorescent protein (POMC-EGFP) mice (postnatal day 21) were exposed to 3% sevoflurane for 6 h. Following exposure, cleaved caspase 3, expression of EGFP and differential maturational markers were quantified and compared with unanesthetized littermates. Electrophysiological properties of EGFP+ and EGFP− cells in the subgranular zone and the inner half of the granule cell layer were recorded by whole-cell patch-clamp. We found that sevoflurane significantly increased apoptosis of POMC-EGFP+ granule cells that accounted for approximate 1/3 of all apoptotic cells in dentate gyrus. Apoptotic EGFP− granule cells more frequently expressed the immature neuronal marker calretinin (75.4% vs 45.0%, P
Databáze: OpenAIRE