Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY 13902, USA.
Neurobiol Learn Mem. 2011 Nov;96(4):596-608. doi: 10.1016/j.nlm.2011.01.003. Epub 2011 Jan 21.
Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone.
慢性酒精中毒与认知功能障碍有关。超过 75%的尸检慢性酒精中毒者有明显的大脑损伤，超过 50%的戒酒者表现出某种程度的学习和记忆障碍。然而，不同病因因素对酒精相关神经病理学和认知障碍发展的相对贡献仍存在争议。造成这种困境的一个原因是，酒精毒性和硫胺素缺乏都会导致大脑损伤和认知问题。两种与酒精相关的神经紊乱，即酒精相关性痴呆和韦尼克-科尔萨科夫综合征，在啮齿动物中得到了建模。这些临床前模型阐明了乙醇毒性和硫胺素缺乏对痴呆和健忘症发展的相对贡献。在这些模型中观察到的——从反复和慢性乙醇暴露到硫胺素缺乏——是神经和认知失调的进展。反复 binge 暴露于乙醇会通过减少 GABA 能抑制和促进谷氨酸能兴奋来改变神经可塑性，长期慢性乙醇暴露会导致海马和皮质细胞丢失，以及海马神经生长因子蛋白含量减少，这对神经存活至关重要，而硫胺素缺乏会导致间脑的大体病理损伤、神经生长因子蛋白水平降低，以及海马和皮质中的神经递质水平降低。行为上，在反复或慢性乙醇暴露后恢复后，工作或情景记忆受损，长时间戒酒后可能会恢复。相比之下，在硫胺素缺乏后，会出现严重和持久的空间记忆障碍和增加的持续行为。除了白质减少外，乙醇和硫胺素缺乏之间的相互作用不会产生比长期单独缺乏硫胺素更多的行为或神经病理学。
