Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

Abstract

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Evaluation of Varied Modalities of Tocotrienol Supplementations to Counter the Cerebellar Oxidative Stress Caused by Low-to-moderate Doses of Ethanol in Rats

“…Variations any alteration in cerebellar mass. [4] No change in absolute cerebellar mass or cerebello-somatic index (absolute cerebellum weight / body weight) was also observed in the current study (data not shown). Even in chronic exposure, Et was ineffective to alter the brain weight while body weights were significantly less compared to control animals.…”

“…[5] Along with other brain regions, cerebellum faces neuronal loss in chronic Et exposure and this may have a relationship with loss of cognitive and motor functions. [4,6,7] In fact, compared to cerebral cortex, Et-induced apoptosis was higher in cerebellum. [8] Cerebellum, per se, is highly vulnerable to chronic Et exposure; nevertheless, the extent of damage depends on the profile of the subject as well as level of consumption.…”

“…[15,33] In addition to oxidative stress, cerebellar excytotoxicity, inflammation as well as apoptosis of cerebellar neurons were reported in response to Et exposure. [4] In this context, supplementation with T3 would have been an ideal curative measure as antioxidant, anti-inflammatory and neuroprotective roles of it are well known. [34] While, T3 was found to be useful against oxytosis, the neuroprotective efficacy was observed only when administered before predictable cerebral ischemia.…”

“…[3] On the other hand, adolescents face relatively less motor impairments and this indulges them towards frequent self-intoxication and dependence on alcohol. [4] This, in turn, raises the overall years of alcohol consumption and changes the social binge drinkers into chronic drinkers. Not only India, being the most used psychoactive drug, alcohol abuse is a grave health problem worldwide and remains in top five causes of death in many countries.…”

Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation

“…In this test, the animal’s ability to maintain postural stability was evaluated [ 70 , 71 , 72 ]. Animals with impaired motor coordination and equilibrium are unable to perform descent and ascent movements on a bar with a slope greater than 45°.…”