Parkin immunoreactivity in the brain of human and non-human primates: An immunohistochemical analysis in normal conditions and in Parkinsonian syndromes

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against h uman parkin. Immunohistochemical analysis showed that parkin is expressed i n neuronal perikarya and processes but also in glial and blood vessels in t he primate brain (human and monkey). Electron microscopy indicated that par kin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneous ly in various structures of the brain. It was detectable in the dopaminergi c systems at the level of the perikarya in the mesencephalon but also in th e striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hipp ocampal formation, the pallidal complex, the red nucleus and the cerebellum . Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-i ntoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergi c neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminerg ic neurons in familial cases of Parkinson's disease with autosomal recessiv e transmission cannot be explained solely in terms of an alteration of this protein. J. Comp. Neurol. 432: 184-196, 2001. (C) 2001 Wiley-Liss, Inc.