Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum

Abstract

The adverse effects of acute and chronic ethanol exposure on cerebellar functions have been acknowledged for decades, in terms of impaired control of movement and balance. In addition to the motor impairment, cerebellar degeneration has recently been shown to contribute to distinct neuropsychological deficits in chronic alcoholics, as well as in children with prenatal ethanol exposure. The basic mechanisms underlying these ethanol-induced functional alterations and the related neuropathology in the cerebellum have mostly been clarified only recently. These mechanisms include: (i) excitotoxicity; (ii) dietary factors, especially thiamine depletion; (iii) glial abnormalities; (iv) changes in growth factors; (v) apoptotic mechanisms; (vi) oxidative stress; and (vii) compromised energy production. Although these mechanisms widely apply not only to the mature cerebellum, but also to the developing and the aging cerebella, the developing and the aged cerebellum have some special characteristics, which may make them even more vulnerable to ethanol-induced degeneration. These special instances will be discussed along with the general mechanisms of ethanol-induced cerebellar degeneration.

Adult onset sporadic ataxias: a diagnostic challenge

“…The pathogenesis of alcoholic cerebellar degeneration includes both: the direct toxic effect of the alcohol to the cerebellum and the consequences of vitamin B1 (thiamine) deficiency. Alcohol produces a toxic effect to Purkinje cells, and also is responsible for inhibitory mechanisms in GABA system, increases lipid peroxidation, and reduces of antioxidant concentrations [7][8][9] . Alcoholics have thiamine deficiency as a result of poor diet, gastrointestinal disorders and liver disease 1 .…”

Original article Alcohol-induced changes in the developing cerebellum. Ultrastructural and quantitative analysis of neurons in the cerebellar cortex

“…Factors that disrupt the normal development of the cerebellum can cause different effects, depending on the developmental stage [16], which may be the reason for discrepancies in the results obtained by different researchers in the study of structural and functional ethanol-induced deficits in the cerebellum [11,18].…”

Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

“…1 The deleterious consequence of alcohol in the brain includes a direct toxic effect on Purkinje cells, an inhibitory role in the GABA neurogenic system, and the induction of lipid peroxidation which causes a reduction in the level of antioxidant concentrations in the brain. 5 The loss of neurones in alcoholics is potentiated by vitamin B1 defi ciency which results from a poor diet, a common feature with alcoholics. 6 This degenerative cascade included the direct toxic effect of vitamin B1 metabolism.…”