Cerebellar [ 3H]inositol 1,4,5-trisphosphate binding is markedly decreased in human olivopontocerebellar atrophy

Abstract

We examined the behaviour of [ 3H]inositol-1,4,5-trisphosphate (IP 3) binding in autopsied cerebellar and cerebral cortex of 10 neurologically normal controls and 8 patients with end-stage olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder characterized histologically by severe degeneration of Purkinje cells. [ 3H]IP 3 binding to normal human cerebellar cortex was 6–15 times higher than in cerebral cortex. As compared with the controls, mean [ 3H]IP 3 binding to cerebellar cortex was markedly reduced by 61% in the OPCA patients whereas levels were normal in frontal and occipital cortices. Since the Purkinje cell dendrite receives neuronal input from granule cells and climbing fibers utilizing glutamate and aspartate, respectively, as neurotransmitters, the reduced IP 3 binding in OPCA cerebellar cortex may reflect a loss of Purkinje cells containing these excitatory amino acid receptors linked to the phosphatidylinositide second messenger system. Our data suggest that in humans, IP 3 receptors may be highly localized to the Purkinje cell dendrite.