engleski

Developmental brain disorders during cytomegaloviral infection

Cytomegalovirus (CMV) is the most significant infectious cause of congenital abnormalities of the central nervous system including retardation, microcephaly, cerebellar atrophy, hearing loss and blindness. The pathogenesis of a viral infection has not been fully elucidate yet and it may arise either because of direct viral damage to neuronal cells or indirectly because of different humoral factors. We have established a model of murine CMV (MCMV) brain infection in newborn mice. We used this model to study neuronal development after MCMV infection and have focused our analysis to the cerebellum because the majority of its cells mature postnatally making it accessible for our examination. Cerebellum has distinct cytoarchitecture and migration pattern of its neuronal cells has been well defined so every developmental disruption is easy to follow. Newborn mice have been infected intraperitoneally with MCMV. The viral presence in the brain has been analysed by plaque assay on murine embrional fibroblasts. Histological evaluation and immunostaining for different neuronal population was used to detect disturbance in cerebellar development. Mice infected with MCMV consistently showed several abnormalities. The development of cerebellar folia was defective. The position and number of folia was not altered but they expressed delay in growth. Whole cerebellar area, as well as volume, was reduced in size throughout cerebellar development. In infected animals significant delay in granule cell migration from external granular layer (EGL) to internal granular layer (IGL) was detected. Purkinje cell (PC) loss was observed in all stages of postnatal development. Moreover an ectopic PC located in IGL was observed after calbindin staining. Our results revealed marked impairment in neuronal migration and maturation indicating that MCMV infection has multiple influence in neuronal development.

MCMV; brain disorders

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