Characteristics of neurons and glia in the brain of Fukuyama type congenital muscular dystrophy.

Fukuyama type congenital muscular dystrophy accompanies central nervous system and ocular lesions. Morphological findings suggest that major central nervous system lesions, such as cortical dysplasia, are caused by the abnormal glia limitans due to an impairment of astrocytes. Increase of corpora amylacea and neurofibrillary tangles suggests acceleration of the aging process in the Fukuyama type congenital muscular dystrophy brain. Glycosylation of alpha-dystroglycan is decreased in the central nervous system of Fukuyama type congenital muscular dystrophy in a similar manner to the skeletal muscle, but dystroglycan mRNA levels appear to be increased. Glycosylated alpha-dystroglycan is reduced in the glia limitans formed by astrocytic endfeet. Slight accumulation of N(epsilon)-(carboxymethyl)lysine, an oxidative modification product, is observed in astrocytes of Fukuyama type congenital muscular dystrophy and in an astrocytoma cell line with suppressed fukutin expression. Cerebral cortical neurons of Fukuyama type congenital muscular dystrophy and controls react with an antibody for core alpha-dystroglycan but not with an antibody for glycosylated alpha-dystroglycan. Carboxymethyl lysine is accumulated in cortical neurons of a severe case of Fukuyama type congenital muscular dystrophy. Both astrocytes and neurons appear to be sensitive to oxidative stress when fukutin is suppressed. However, it is still unclear how the loss of fukutin causes astrocytic and neuronal dysfunction. Since the central nervous system is composed of several components that are closely related to each other, more investigations are needed for thorough understanding of the Fukuyama type congenital muscular dystrophy brain. Moreover, since astrocytes and epithelial cells may show different cellular responses to fukutin suppression, it seems important to evaluate the functions of fukutin in each type of cell or tissue, not only to prove the pathogenesis of Fukuyama type congenital muscular dystrophy, but also for applying appropriate therapies, especially those at molecular level.