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      The Inferior Colliculus in Alcoholism and Beyond

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          Abstract

          Post-mortem neuropathological and in vivo neuroimaging methods have demonstrated the vulnerability of the inferior colliculus to the sequelae of thiamine deficiency as occurs in Wernicke-Korsakoff Syndrome (WKS). A rich literature in animal models ranging from mice to monkeys—including our neuroimaging studies in rats—has shown involvement of the inferior colliculi in the neural response to thiamine depletion, frequently accomplished with pyrithiamine, an inhibitor of thiamine metabolism. In uncomplicated alcoholism (i.e., absent diagnosable neurological concomitants), the literature citing involvement of the inferior colliculus is scarce, has nearly all been accomplished in preclinical models, and is predominately discussed in the context of ethanol withdrawal. Our recent work using novel, voxel-based analysis of structural Magnetic Resonance Imaging (MRI) has demonstrated significant, persistent shrinkage of the inferior colliculus using acute and chronic ethanol exposure paradigms in two strains of rats. We speculate that these consistent findings should be considered from the perspective of the inferior colliculi having a relatively high CNS metabolic rate. As such, they are especially vulnerable to hypoxic injury and may be provide a common anatomical link among a variety of disparate insults. An argument will be made that the inferior colliculi have functions, possibly related to auditory gating, necessary for awareness of the external environment. Multimodal imaging including diffusion methods to provide more accurate in vivo visualization and quantification of the inferior colliculi may clarify the roles of brain stem nuclei such as the inferior colliculi in alcoholism and other neuropathologies marked by altered metabolism.

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          Most cited references418

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          Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III.

          National epidemiologic information from recently collected data on the new DSM-5 classification of alcohol use disorder (AUD) using a reliable, valid, and uniform data source is needed.
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            A clinicopathological study of autism.

            A neuropathological study of autism was established and brain tissue examined from six mentally handicapped subjects with autism. Clinical and educational records were obtained and standardized diagnostic interviews conducted with the parents of cases not seen before death. Four of the six brains were megalencephalic, and areas of cortical abnormality were identified in four cases. There were also developmental abnormalities of the brainstem, particularly of the inferior olives. Purkinje cell number was reduced in all the adult cases, and this reduction was sometimes accompanied by gliosis. The findings do not support previous claims of localized neurodevelopmental abnormalities. They do point to the likely involvement of the cerebral cortex in autism.
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              Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome.

              The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.
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                Author and article information

                Contributors
                Journal
                Front Syst Neurosci
                Front Syst Neurosci
                Front. Syst. Neurosci.
                Frontiers in Systems Neuroscience
                Frontiers Media S.A.
                1662-5137
                11 December 2020
                2020
                : 14
                : 606345
                Affiliations
                [1] 1Neuroscience Program, SRI International , Menlo Park, CA, United States
                [2] 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine , Stanford, CA, United States
                Author notes

                Edited by: James W. Grau, Texas A&M University, United States

                Reviewed by: Erik Oudman, Slingedael Korsakoff Center, Rotterdam, Netherlands; Jorge Kattah, University of Illinois at Chicago, United States

                *Correspondence: Natalie M. Zahr, nzahr@ 123456stanford.edu

                This article was submitted to Systems Neuroscience, a section of the journal Frontiers in Systems Neuroscience

                Article
                10.3389/fnsys.2020.606345
                7759542
                33362482
                e2e4d151-843d-488f-af1f-fac33683d061
                Copyright © 2020 Bordia and Zahr.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 September 2020
                : 02 November 2020
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 418, Pages: 19, Words: 0
                Funding
                Funded by: National Institute on Alcohol Abuse and Alcoholism 10.13039/100000027
                Funded by: National Institute on Alcohol Abuse and Alcoholism 10.13039/100000027
                Funded by: National Institute on Alcohol Abuse and Alcoholism 10.13039/100000027
                Categories
                Neuroscience
                Review

                Neurosciences
                wernicke’s encephalopathy,korsakoff’s syndrome,metabolism,energy,ethanol
                Neurosciences
                wernicke’s encephalopathy, korsakoff’s syndrome, metabolism, energy, ethanol

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