Early protein malnutrition disrupts cerebellar development and impairs motor coordination

Maternal malnutrition affects every aspect of fetal development. The present study asked the question whether a low-protein diet of the mother could result in motor deficits in the offspring. Further, to examine whether cerebellar pathology was correlated with motor deficits, several parameters of the postnatal development of the cerebellum were assayed. This is especially important because the development of the cerebellum is unique in that the time scale of development is protracted compared with that of the cortex or hippocampus. The most important result of the study is that animals born to protein-deficient mothers showed significant delays in motor development as assessed by rotarod and gait analysis. These animals also showed reduced cell proliferation and reduced thickness in the external granular layer. There was a reduction in the number of calbindin-positive Purkinje cells (PC) and granular cells in the internal granular layer. However, glial fibrillary acidic protein-positive population including Bergmann glia remained unaffected. We therefore conclude that the development of the granular cell layer and the PC is specifically prone to the effects of protein malnutrition potentially due to their protracted developmental period from approximately embryonic day 11 to 13 until about the third postnatal week.