Calcium signaling molecules in human cerebellum at midgestation and in ataxia.

Abstract

A fundamental question in brain development is how neurons make the precise topographic connections necessary for function. The hypothesis that transient expression of calcium (Ca2+) signaling molecules may have a role in this process was tested by studying human cerebella at midgestation. In addition, four adult brains, two controls and two from patients with ataxia, were studied as well. The temporal and spatial distribution of intracellular Ca2+ channel/receptors, inositol trisphosphate receptor type 1 (IP3R1) and ryanodine receptor (RyR) and three Ca2+ binding proteins were examined with immunocytochemical methods. A positive immune reaction with all markers of Ca2+ signaling was found in the Purkinje cell layer starting from 17 g.w. (gestational weeks), the youngest age studied. The immune reactions were not homogeneous throughout the extent of the Purkinje cell layer, but instead displayed a 'patchy' appearance in all intrauterine stages. In the adult cerebellum the expression of Ca2+ signaling molecules was homogenous. In the two cerebella obtained from patients suffering from ataxia, a several-fold reduction of immunostaining with IP3R1 was found. Our findings suggest that transient and differential mobilization of intracellular Ca2+ in seemingly homogenous neuronal types may play a role in development of highly organized projection maps of the cerebellar cortex. Moreover, lack of IP3R1 in the diseased brains suggests that internal stores of Ca2+ play an important role in normal function of the cerebellum.