1 INMED-INSERM, Aix-Marseille University, Marseille, France.
2 Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia.
Neuroscientist. 2018 Apr;24(2):130-141. doi: 10.1177/1073858417712667. Epub 2017 Jun 5.
Ethanol induces massive neuroapoptosis in the developing brain. One of the main hypotheses that has been put forward to explain the deleterious actions of ethanol in the immature brain involves an inhibition of neuronal activity. Here, we review recent evidence for this hypothesis obtained in the somatosensory cortex and hippocampus of neonatal rodents. In both structures, ethanol strongly inhibits brain activity. At the doses inducing massive neuroapoptosis, ethanol completely suppresses the early activity patterns of spindle-bursts and gamma oscillations in the neocortex and the early sharp-waves in the hippocampus. The inhibitory effects of ethanol decrease with age and in adult animals, ethanol only mildly depresses neuronal firing and induces delta-wave activity. Suppression of cortical activity in neonatal animals likely involves inhibition of the myoclonic twitches, an important physiological trigger for the early activity bursts, and inhibition of the thalamocortical and intracortical circuits through a potentiation of GABAergic transmission and an inhibition of N-methyl-d-aspartate (NMDA) receptors, that is in keeping with the neuroapoptotic effects of other agents acting on GABA and NMDA receptors. These findings provide support for the hypothesis that the ethanol-induced inhibition of cortical activity is an important pathophysiological mechanism underlying massive neuroapoptosis induced by ethanol in the developing brain.
乙醇在发育中的大脑中诱导大量神经细胞凋亡。为了解释乙醇在未成熟大脑中的有害作用，提出了一个主要假说，即抑制神经元活性。在这里，我们综述了在新生啮齿动物的体感皮层和海马体中获得的这一假说的最新证据。在这两个结构中，乙醇强烈抑制大脑活动。在诱导大量神经细胞凋亡的剂量下，乙醇完全抑制了新皮层中的纺锤波爆发和γ振荡以及海马中的早期尖波。乙醇的抑制作用随年龄的增长而降低，在成年动物中，乙醇仅轻度抑制神经元放电并诱导δ波活动。新生动物皮层活动的抑制可能涉及对肌阵挛抽搐的抑制，肌阵挛抽搐是早期活动爆发的重要生理触发因素，以及通过增强 GABA 能传递和抑制 N-甲基-D-天冬氨酸 (NMDA) 受体来抑制丘脑皮质和皮质内回路，这与其他作用于 GABA 和 NMDA 受体的药物的神经细胞凋亡作用一致。这些发现为以下假说提供了支持：即乙醇诱导的皮层活动抑制是乙醇在发育中的大脑中诱导大量神经细胞凋亡的重要病理生理学机制。
