Distribution and immunohistochemical characterization of torsinA immunoreactivity in rat brain

A mutation of the DYT1 gene on chromosome 9q34 has recently been identified as the cause of one form of autosomal-dominantly inherited dystonia. Torsi nA, the protein product of this gene, has homology with the family of heat shock proteins, and is found in many peripheral tissues and brain regions. We used a polyclonal antibody to torsinA, developed in our laboratory, to s ystematically examine the regional distribution of torsinA in rat brain. We find that neurons in all examined structures are immunoreactive for this p rotein. There is intense immunoreactivity in most neuronal nuclei, with sli ghtly less labeling of cytoplasm and proximal processes. Terminals also are labeled, especially in striatum, neocortex and hippocampus. Double-labelin g fluorescence immunohistochemistry using antibodies to neurotransmitters a nd other neurochemical markers demonstrated that the majority of neurons of all studied neurochemical types are immunoreactive for torsinA. Our findin gs indicate that torsinA is widely distributed in the central nervous syste m implicating additional, localized factors, perhaps within the basal gangl ia, in the development of dystonia. Many other proteins have a similar wide spread distribution, including some which have been implicated in other mov ement disorders and neurodegenerative processes, such as parkin, alpha -syn uclein. ubiquitin and huntingtin. The distribution of torsinA in rat brain as demonstrated by immunohistochemistry contrasts with the results of in si tu hybridization studies of torsinA mRNA in human postmortem brain in which a more limited distribution was found. (C) 2001 Elsevier Science B.V. All rights reserved.