Distribution and ultrastructural localization of torsinA immunoreactivity in the human brain

• Published in: Brain research 2003-10, Vol.986 (1), p.12-21
• Main Authors: Augood, Sarah J., Keller-McGandy, Christine E., Siriani, Ana, Hewett, Jeffrey, Ramesh, Vijaya, Sapp, Ellen, DiFiglia, Marion, Breakefield, Xandra O., Standaert, David G.
• Format: Article
• Language: English
• Subjects: Animals; Axonal transport; Biological and medical sciences; Brain - metabolism; Brain - ultrastructure; Carrier Proteins - metabolism; Dendrites - metabolism; Dendrites - ultrastructure; Diseases of striated muscles. Neuromuscular diseases; Dopamine; dystonia; DYT1; Humans; Immunohistochemistry; Macaca; Macaca fascicularis; Medical sciences; Microscopy, Electron; Molecular Chaperones; Neostriatum - metabolism; Neostriatum - ultrastructure; Neurology; Parkinson’s disease; Presynaptic Terminals - metabolism; Presynaptic Terminals - ultrastructure; Recombinant Fusion Proteins - immunology; Synaptic Transmission - physiology; Synaptic Vesicles - metabolism; Synaptic Vesicles - ultrastructure; TOR1A
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)03164-0

We have examined the distribution and ultrastructural localization of torsinA, the protein product of the TOR1A gene, in the normal adult human and Macaque brain. TorsinA immunoreactivity was visualized using a monoclonal antibody raised against a fusion protein encoding exon 4 of human torsinA. Western blot analysis of brain homogenates revealed a major species of about 39 kDa, consistent with the predicted size of glycosylated torsinA protein. By light microscopy, torsinA like-immunoreactivity was enriched in gray matter in all brain regions examined. Immunoreactivity was concentrated in the neuropil and immunopositive cell bodies were not observed. Structures particularly enriched in torsinA like-immunoreactivity included the cerebral cortex, the caudate-putamen, globus pallidus, the hippocampal formation, the thalamus, the substantia nigra and molecular cell layer of the cerebellar cortex. Cell bodies of pigmented dopamine neurons in the substantia nigra pars compacta were immunonegative. Biochemical fractionation of the human striata revealed a concentration of torsinA immunoreactivity in particulate fractions. Ultrastructural studies of the human and Macaque striata further revealed an association of torsinA immunostaining with small vesicles within axons and presynaptic terminals forming symmetric synapses. These ultrastructural studies are consistent with a pre-synaptic localization of torsinA protein in the adult striatum and are consistent with a role of torsinA in modulating striatal signaling, although the widespread localization of the protein suggests it probably also participates in signaling in other regions.