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Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease

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Abstract

Immunohistochemistry using both a newly developed polyclonal, and a commercially available monoclonal, anti-insulin receptor antibody was done on the midbrain from cases of idiopathic Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, vascular parkinsonism and non-neurological controls. Both antibodies gave indentical patterns of neuronal staining. The neurons of the oculomotor nucleus were immunopositive in all the brains. However, the neurons in the pars compacta of the substantia nigra, paranigral nucleus, parabrachial pigmental nucleus, tegmental pedunculopontine nucleus, supratrocheal nucleus, cuneiform nucleus, subcuneiform nucleus and lemniscus medialis, which were positive in other diseases and in non-neurological controls, were not stained by these antibodies in PD brains. These results suggest that, in PD, a dysfunction of the insulin/insulin receptor system may precede death of the dopaminergic neurons.

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References

  1. Appel SH (1981) A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. Ann Neurol 10: 499–505

    Google Scholar 

  2. Baskin DG, Figlewicz DP, Woods SC, Porte D Jr, Dorsa DM (1987) Insulin in the brain. Annu Rev Physiol 49: 335–347

    Google Scholar 

  3. Bhat NR (1983) Insulin dependent neurite outgrowth in cultured embryonic mouse brain cells. Dev Brain Res 11: 315–318

    Google Scholar 

  4. Boyd FT Jr, Clarke DW, Muther TF, Raizada MK (1985) Insulin receptors and insulin modulation of norepinephrine uptake in neuronal cultures from rat brain. J Biol Chem 260: 15880–15884

    Google Scholar 

  5. Brief DJ, Davis JD (1984) Reduction of food intake and body weight by chronic intraventricular insulin infusion. Brain Res Bull 12: 571–575

    Google Scholar 

  6. Clarke DW, Boyd FT, Kappy MS, Raizada MK (1985) Insulin stimulates macromolecular synthesis in cultured glial cells from rat brain. Am J Physiol 249: C484-C489

    Google Scholar 

  7. Corp ES, Woods SC, Porte D Jr, Dorsa DM, Figlewicz DP, Baskin DG (1986) Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci Lett 70: 17–22

    Google Scholar 

  8. Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou JH, Masiarz F, Kan YW, Goldfine ID, Roth RA, Rutter WJ (1985) The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell 40: 747–758

    Google Scholar 

  9. Gaul G, Lübbert H (1992) Cortical astrocytes activated by basic fibroblast growth factor secrete molecules that stimulate differentiation of mesencephalic dopaminergic neurons. Proc R Soc Lond 249: 57–63

    Google Scholar 

  10. Hefti F, Michel PP, Knusel B (1990) Neurotrophic factors and Parkinson's disease. Adv Neurol 53: 123–127

    Google Scholar 

  11. Heidenreich KA, Zahniser NR, Berhanu P, Brandenburg D, Olefsky JM (1983) Structural differences between insulin receptors in the brain and peripheral target tissues. J Biol Chem 258: 8527–8530

    Google Scholar 

  12. Hill JM, Lesniak MA, Pert CB, Roth J (1986) Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience 17: 1127–1138

    Google Scholar 

  13. Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350: 230–232

    Google Scholar 

  14. Izumi Y, Pinard E, Roussel S, Seylaz J (1992) Insulin protects brain tissue against focal ischemia in rats. Neurosci Lett 144: 121–123

    Google Scholar 

  15. Knusel B, Michel PP, Schwaber JS, Hefti F (1990) Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J Neurosci 10: 558–570

    Google Scholar 

  16. LeRoith D, Lowe WL Jr, Shemer J, Raizada MK, Ota A (1988) Development of brain insulin receptors. Int J Biochem 20: 225–230

    Google Scholar 

  17. Olefsky JM (1990) The insulin receptor: a multifunctional protein. Diabetes 39: 1009–1016

    Google Scholar 

  18. Olszewski J, Baxter D (1954) Cytoarchitecture of the human brain stem. Karger, Basel, p 54

    Google Scholar 

  19. Porte D Jr, Woods SC (1981) Regulation of food intake and body weight by insulin. Diabetologia 20: 274–280

    Google Scholar 

  20. Rhoads DE, DiRocco RJ, Osburn LD, Peterson NA, Raghupathy E (1984) Stimulation of synaptosomal uptake of neurotransmitter amino acids by insulin: possible role of insulin as a neuromodulator. Biochem Biophys Res Commun 119: 1198–1204

    Google Scholar 

  21. Roth RA, Morgan DO, Beaudoin J, Sara V (1986) Purification and characterization of the human brain insulin receptor. J Biol Chem 261: 3753–3757

    Google Scholar 

  22. Sauter A, Goldstein M, Engel J, Ueta K (1983) Effects of insulin on central catecholamines. Brain Res 260: 330–333

    Google Scholar 

  23. Spina MB, Squinto SP, Miller J, Lindsay RM, Hyman C (1992) Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system. J Neurochem 59: 99–106

    Google Scholar 

  24. Steinbusch HWM, Vermeulen RJ, Tonnaer JADM (1990) Basic fibroblast growth factor enhances survival and sprouting of fetal dopaminergic cells implanted in the denervated rat caudate-putamen: preliminary observations. Prog Brain Res 82: 81–86

    Google Scholar 

  25. Tooyama I, Kawamata T, Walker D, Yamada T, Hanai K, Kimura H, Iwane M, Igarashi K, McGeer EG, McGeer PL (1993) Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease. Neurology 43: 372–376

    Google Scholar 

  26. Ullrich A, Bell JR, Chen EY, Herrera R, Petruzzelli LM, Dull TJ, Gray A, Coussens L, Liao YC, Tsubokawa M, Mason A, Seeburg PH, Grunfeld C, Rosen OM, Ramachandran J (1985) Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313: 756–761

    Google Scholar 

  27. Unger J, McNeill TH, Moxley III RT, White M, Moss A, Livingston JN (1989) Distribution of insulin receptor-like immunoactivity in the rat forebrain. Neuroscience 31: 143–157

    Google Scholar 

  28. Unger JW, Livingston JN, Moss AM (1991) Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog Neurobiol 36: 343–362

    Google Scholar 

  29. Unger JW, Moss AM, Livingston JN (1991) Immunohistochemical localization of insulin receptors and phosphotyrosine in the brainstem of the adult rat. Neuroscience 42: 853–861

    Google Scholar 

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The work in the Kinsmen Laboratory was supported by the MRC of Canada and the Parkinson Society of Canada

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Moroo, I., Yamada, T., Makino, H. et al. Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease. Acta Neuropathol 87, 343–348 (1994). https://doi.org/10.1007/BF00313602

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  • DOI: https://doi.org/10.1007/BF00313602

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