title: Overexpression of heat shock proteins in pallido-nigral axonal spheroids of nonhuman aged primates.
abstract: The occurrence of spheroids has been described in the globus pallidus (GP) and substantia nigra pars reticulata (SNr) of aged rhesus monkeys. Opinions vary as to the origin of spheroids. Ultrastructural and immunohistochemical analysis suggested that spheroids originate from degenerating axons or astroglia. In the present study, we have investigated the GP and SNr of aged monkeys (Macaca fascicularis and Macaca mulatta). Although immunoreactive for microtubule-associated protein (MAP) 1A, tau, amyloid precursor protein, synaptophysin and phosphorylated neurofilament, spheroids were not immunoreactive for MAP1B and MAP2. We confirmed the axonal nature of pallido-nigral spheroids in aged rhesus monkeys. Pallido-nigral spheroids have been reported to overexpress stress proteins, such as ubiquitin, alphaB-crystallin, and heat shock protein (Hsp) 27. We further evaluated the expression of Hsps in pallido-nigral spheroids. As well as being intensely immunoreactive for ubiquitin, alphaB-crystallin, Hsp27, and Hsp70, spheroids were immunoreactive for Hsp32 (heme oxygenase-1), Hsp40, Hsp60, and Hsp90. On the basis of these findings, we speculate that Hsp32-immunoreactive spheroids might be expressed as an oxidative stress response. Induction of other Hsps might play a role in protection of axons from the aggregation of neurofilament, MAPs and other proteins, and failure to protect degenerating axons might result in their proteolysis by the ubiquitin-proteasome system.
authors.affiliation: Division of Neuropathology, Department of Neuroscience, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, 105-8461, Tokyo, Japan. fukuda-t@jikei.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furuhata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Takao
authors.initials: T
authors.lastname: Oishi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ogihara
authors.forename: Jun
authors.initials: J
authors.lastname: Kubota
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Azuma
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Umemura
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008251:Macaca; D008297:Male; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D006360:Heat-Shock Proteins