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Calcineurin in human brain and its relation to extrapyramidal system

Immunohistochemical study on postmortem human brains

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Summary

Calcineurin immunoreactivity has been successfully detected in formalin-fixed paraffinembedded postmortem human brain tissue using the peroxidase-antiperoxidase method. We have examined two autopsy cases with Huntigton's disease (HD), three cases with Parkinson's disease, and two senile patients as controls. In the controls, calcineurin immunoreactivity was present in neuronal cells only and highly concentrated in the caudate nucleus, putamen, globus pallidus (striato-pallidal pathway), substantia nigra (striato-nigral pathway) and hippocampal formation. These localizations were similar to those identified in rat brain. There was a marked depletion of neurons containing calcineurin in the caudate nucleus and putamen, and a marked reduction of calcineurin-immunoreactive nerve fibers in the globus pallidus and substantia nigra were found in the cases with HD, but not in those with Parkinson's disease. These findings suggest that calcineurin can be a useful and specific index of neuronal degeneration in the caudato-putamen resulting from extrapyramidal diesease, and that the calcineurin-immunostaining method can be a valuable tool for clarifying the anatomy of the human extrapyramidal system.

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References

  • Brownstein MJ, Morz EA, Tappaz L, Leeman SE (1977) On the origin of substance P and glutamic acid decarboxylase (GAD) in the substantia nigra. Brain Res 135:315–323

    Google Scholar 

  • Bruyn GW (1968) Diseases of basal ganglia. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 6. North Holland, Amsterdam, pp 298–378

    Google Scholar 

  • Forno LS (1982) Pathology of Parkinson's disease. In: Marsden CD, Fahn S (eds) Movement disorders, vol 2. Butterworth Scientific, London, pp 25–40

    Google Scholar 

  • Goto S, Yamamoto H, Fukunaga K, Iwasa T, Matsukado Y, Miyamoto E (1985) Dephosphorylation of microtubule-associated protein 2, tau factor, and tubulin by calcineurin. J Neurochem 45:276–283

    Google Scholar 

  • Goto S, Matsukado Y, Mihara Y, Inoue N, Miyamoto E (1986a) Calcineurin as a neuronal marker of human brain tumors. Brain Res 371:237–243

    Google Scholar 

  • Goto S, Matsukado Y, Mihara Y, Inoue N, Miyamoto E (1986b) The distribution of calcineurin in rat brain by light and electron microscopic immunohistochemistry and enzyme-immunoassay. Brain Res (in press)

  • Hemmings HC Jr, Greengard P, Tung HYL, Cohen P (1984) DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature 310:503–505

    Google Scholar 

  • Klee CB,Crough TH, Krinks MH (1979) Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci USA 76:6270–6273

    Google Scholar 

  • Klee CB, Krinks MH, Manalan AS, Cohen P, Stewart AA (1983) Isolation and characterization of bovine brain calcineurin: a calmodulin-stimulated protein phosphatase. Methods Enzymol 102:227–244

    Google Scholar 

  • Krinks MH, Manalan AS, Klee CB (1985) Calcineurin: a brain-specific isozyme of protein phosphatase-2B. Fed Proc 1743:707

    Google Scholar 

  • Pallen CJ, Wang H (1983) Calmodulin-stimulated dephosphorylation ofp-nitrophosphate and free phosphotyrosine by calcineurin. J Biol Chem 258:8550–8553

    Google Scholar 

  • Sternberger LA, Hardy PH, Cuculis JJ, Meter HG (1970) The unlabelled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase — antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:314–333

    Google Scholar 

  • Stewart AA, Ingebritsen TS, Manalan A, Klee CB, Cohen P (1982) Discovery of Ca2+-and calmodulin-dependent protein phosphatase. Probable identity with calcineurin (CaM-BP80). FEBS Lett 137:80–84

    Google Scholar 

  • Stewart AA, Ingebristen TS, Cohen P (1983) The protein phosphatase involved in cellular regulation. 5. Purification and properties of a Ca2+/calmodulin-dependent protein phosphatase (2B). Eur J Biochem 132:289–295

    Google Scholar 

  • Tonks NK, Cohen P (1983) Calcineurin is a calcium ion dependent, calmodulin-stimulated protein phosphatase. Biochim Biophys Acta 747:191–193

    Google Scholar 

  • Wallace RW, Tallant EA, Cheung WY (1980) High levels of a heat-labile calmodulin-binding protein (CaM-BP80) in bovine neostriatum. Biochemistry 19:1831–1837

    Google Scholar 

  • Wood JG, Wallace RW, Whitaker JN, Cheung WY (1980) Immunohistochemical localization of calmodulin and a heatlabile calmodulin-binding protein (CaM-BP80) in basal ganglia of mouse brain. J Cell Biol 84:66–76

    Google Scholar 

  • Yang SD, Tallant EA, Cheung WY (1982) Calcineurin is a calmodulin-dependent protein phosphatase. Biochem Biophys Res Commun 106:1419–1425

    Google Scholar 

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Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Eductation, Science, and Culture of Japan

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Goto, S., Matsukado, Y., Mihara, Y. et al. Calcineurin in human brain and its relation to extrapyramidal system. Acta Neuropathol 72, 150–156 (1986). https://doi.org/10.1007/BF00685977

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  • DOI: https://doi.org/10.1007/BF00685977

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