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

Fernando B R Da Silva,Mayara A Barros,Rafael R Lima,Paula C Ribera,Rui D Prediger,Enéas A Fontes-Júnior,Sabrina C Cartágenes,Polyane A Cunha,Francisco B Teixeira,Cristiane S F Maia,Luanna M P Fernandes

doi:10.3389/fnbeh.2018.00088

Fernando B R Da Silva, Mayara A Barros + Show 9 more

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https://doi.org/10.3389/fnbeh.2018.00088

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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.

Highlights

Ethanol is one of the most widely used psychoactive drugs in the world (Room et al, 2005)
In line with this idea, for the first time, in the current study we investigated whether heavy chronic ethanol exposure during late adolescence to adulthood may induce motor impairments through a battery of behavioral tasks related to cerebellar function, as well as morphological and cellular alterations in the cerebellum of female rats
To evaluate the effect of chronic ethanol administration during adolescence on motor learning, we subjected the animals to five consecutive sessions (8 rpm) on the rotarod apparatus (Figure 1C)

Summary

Introduction

Ethanol is one of the most widely used psychoactive drugs in the world (Room et al, 2005) Some characteristics, such as the low cost, availability and easy access, contribute to high ethanol consumption among adolescents (Zarzar et al, 2012). It is well documented that ethanol is more deleterious to the brain during adolescence, probably because many CNS structures are under maturation, with changes ranging from molecular components to brain weight (Toga et al, 2006) In this context, previous studies have shown cerebellar atrophy and neurodegeneration following ethanol intoxication (Pierce et al, 1999; Huang et al, 2012), with the ethanol’s deleterious effects been largely influenced by the exposure period and subjects’ ages. The cerebellum, located posterior to the pons and medulla oblongata and interior to the occipital lobes of the cerebral hemisphere, is important for fine motor coordination and motor learning (Lamont and Weber, 2012). Pascual et al (2007) showed that rats exposed to ethanol during the preadolescent and adolescent periods displayed long-term motor impairments in adulthood due to the ethanol-induced cerebellar damage

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