Abstract

Cortical dysplasias are alterations in the organization of the layers of the brain cortex due to problems in neuronal migration during development. The neuronal component has been widely studied in experimental models of cortical dysplasias. In contrast, little is known about how glia are affected. In the cerebellum, Bergmann glia (BG) are essential for neuronal migration during development, and in adult they mediate the control of fine movements through glutamatergic transmission. The aim of this study was to characterize the morphology and intracellular calcium dynamics of BG and astrocytes from mouse cerebellum and their modifications in a model of cortical dysplasia induced by carmustine (BCNU). Carmustine-treated mice were affected in their motor coordination and balance. Cerebellar dysplasias and heterotopias were more frequently found in lobule X. Morphology of BG cells and astrocytes was affected, as were their spontaneous [Ca2+]i transients in slice preparation and in vitro.

Highlights

  • Cortical dysplasia is a type of brain developmental disorder that is frequently associated with clinical manifestations such as epileptic seizures [1]

  • In our previous report we found that carmustine induces dramatic changes in the organization of the cell layers of the cerebellum and in Bergmann glia (BG) cells

  • To determine the effect of carmustine on behaviors associated with the cerebellum, we evaluated glial fibrillary acidic protein (GFAP)-eGFP male mice 30 days after they were born (P30) by the accelerated rotarod motor test, which is widely used to monitor altered cerebellar motor function [37,38,39]

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Summary

Introduction

Cortical dysplasia is a type of brain developmental disorder that is frequently associated with clinical manifestations such as epileptic seizures [1]. It is characterized by abnormal organization of the layers of the brain and the presence of heterotopias—clusters of cells that are not necessarily dysfunctional but rather in abnormal positions. Genetic and acquired factors give rise to cortical dysplasia and affect cell proliferation, migration and maturation during early development [2,3]. There is scant information on cortical dysplasias in the cerebellum. The neuronal component has been widely studied in experimental models of cortical dysplasia. Heterotopic neurons have an increased response to

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