Acta Neuropathologica

, Volume 110, Issue 2, pp 145–150 | Cite as

Overexpression of heat shock proteins in pallido-nigral axonal spheroids of nonhuman aged primates

  • Takahiro FukudaEmail author
  • Jun Shimizu
  • Hiroshi Furuhata
  • Toshiaki Abe
  • Keiko Shimizu
  • Takao Oishi
  • Makoto Ogihara
  • Jun Kubota
  • Akira Sasaki
  • Kazuaki Sasaki
  • Takashi Azuma
  • Shinichiro Umemura
Regular Paper


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, αB-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, αB-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.


Heat shock proteins Spheroids Globus pallidus Substantia nigra pars reticulata Macaca fascicularis/Macaca mulatta 



This study was supported in part by Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan. We are indebted to Ms. Naoko Takabayashi and Miss. Kumiko Iwabuchi for technical assistance.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Takahiro Fukuda
    • 1
    Email author
  • Jun Shimizu
    • 2
  • Hiroshi Furuhata
    • 3
  • Toshiaki Abe
    • 2
  • Keiko Shimizu
    • 4
  • Takao Oishi
    • 4
  • Makoto Ogihara
    • 5
  • Jun Kubota
    • 5
  • Akira Sasaki
    • 5
  • Kazuaki Sasaki
    • 6
  • Takashi Azuma
    • 6
  • Shinichiro Umemura
    • 6
  1. 1.Division of Neuropathology, Department of Neuroscience, Research Center for Medical SciencesThe Jikei University School of MedicineTokyoJapan
  2. 2.Department of NeurosurgeryThe Jikei University School of MedicineTokyoJapan
  3. 3.Medical Engineering Laboratory, Research Center for Medical SciencesThe Jikei University School of MedicineTokyoJapan
  4. 4.Department of Cellular and Molecular Biology, Primate Research InstituteKyoto UniversityAichiJapan
  5. 5.Hitachi Medical CorporationChibaJapan
  6. 6.Central Research LaboratoryHitachi Ltd.TokyoJapan

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