Partial resistance of ataxin-2-containing olivary and pontine neurons to axotomy-induced degeneration.

Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of a polyglutamine tract in ataxin-2, the SCA2 gene product. In spite of the identification of the genetic defect and the coded protein, the function of wild-type ataxin-2 has not been clarified. In order to identify the possible resistance of ataxin-2-containing neurons to degeneration, we investigated in this study the distribution and the characteristics of cell reaction to axotomy in ataxin-2-positive olivary and pontine neurons in a model of cerebellar damage represented by hemicerebellectomy. We also performed double immunofluorescence studies of ataxin-2 and purinergic receptors to characterize ataxin-2-positive surviving neurons. The present data demonstrated that after axotomy olivary and pontine ataxin-2-expressing neurons survived longer than the ataxin-2-negative cell population. Cell counting performed in the different olivary subdivisions failed to reveal any topographical prevalence in the distribution of ataxin-2-positive neurons. Therefore, the relative resistance to axotomy appears to be an intrinsic property of the ataxin-2 cell population. In addition, the capacity to modify the pattern of purinergic receptor expression in response to damage was present in only one subset of ataxin-2-positive surviving neurons. These data suggest that ataxin-2 is involved in resistance to degeneration phenomena which may be lost after mutation.