DECREASED PARVALBUMIN IMMUNOREACTIVITY IN SURVIVING PURKINJE-CELLS OFPATIENTS WITH SPINOCEREBELLAR ATAXIA-1

The distribution of two calcium-binding proteins, calbindin D28k (CaBP ) and parvalbumin (PV), was investigated by immunohistochemistry in th e brains of three individuals dying of nonneurologic illness and three patients with spinocerebellar ataxia-1 (SCA-1). SCA-1 has recently be en proven to be due to an unstable CAG repeat mutation on chromosome 6 . In the cerebellum of control individuals the Purkinje cells showed s trong immunoreactivity to CaBP. Other cells were CaBP-negative. Parval bumin was highly localized to Purkinje, basket, stellate, and Golgi ce lls. All surviving Purkinje cells in SCA-1 were strongly immunoreactiv e to CaBP. The number of PV-immunoreactive Purkinje cells was markedly reduced in SCA-1. In addition, there was a significant decrease in th e intensity of PV immunostaining within the individual Purkinje cells compared with controls. However, in the hippocampus, temporal cortex, and lateral geniculate scattered PV-positive neurons were seen in SCA- 1 patients, similar to those in controls. The present results suggest that the decreased PV-immunoreactivity in the surviving Purkinje cells in SCA-1 may reflect biochemical alterations preceding Purkinje cell degeneration.