Nicotinic Acetylcholine Receptors are Associated with Ketamine-induced Neuronal Apoptosis in the Developing Rat Retina. (15th April 2018)

• Record Type: Journal Article
• Authors: Gao, Lingqi; Han, Junde; Bai, Jie; Dong, Jing; Zhang, Sen; Zhang, Mazhong; Zheng, Jijian
• Is Part Of: Neuroscience. Volume 376(2018)
• Page Start: 1
• Page End: 12
• Publication Date: 2018-04-15
• Subjects: general anesthetic -- ketamine -- development -- early synchronized spontaneous network activity -- acetylcholine -- apoptosis; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.01.057
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Ketamine stage-dependently blocked spontaneous network activity in rat retina. Ketamine-induced, stage-related neuronal apoptosis in rat retina. Apoptosis induced by nAChR inhibitors was comparable with ketamine. Abstract: Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development. All experiments were performed using acutely dissected whole-mount Sprague–Dawley rat retinas (0–14 postnatal days [P0–P14]). Ketamine reversibly blocked spontaneous network activity in the rat retina from P0 to P9 and irreversibly blocked such activity from P10 to P12. The peak of physiological and ketamine-induced neuronal apoptosis mainly occurred from P7 to P9. Blockade of nicotinic acetylcholine receptors (nAChRs) also induced reversible inhibition of spontaneous network activity from P0 to P7 and extensive neuronal apoptosis in the P7 rat retina, while activation of nAChRs or increases in endogenous ACh levels attenuated ketamine-induced apoptotic responses. Furthermore, blockade of α7-nAChR and ß2-nAChR subtypes induced neuronal apoptosis in the developing retina, while activation of the α7-nAChR subtype attenuated ketamine-induced apoptotic responses. These results demonstrate that ketamine may inhibit early synchronized spontaneous network activity by blocking nAChRs, and that such inhibition may contribute to ketamine-induced neuronal apoptosis in the developing rat retina.