Possibility for neurogenesis in substantia nigra of parkinsonian brain
Kenji Yoshimi PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorYong-Ri Ren MD
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorTatsunori Seki PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Department of Anatomy, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorMasanori Yamada PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorHideki Ooizumi MD
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorMasafumi Onodera MD, PhD
Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Tokyo, Japan
Search for more papers by this authorYuko Saito MD, PhD
Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
Search for more papers by this authorShigeo Murayama MD, PhD
Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
Search for more papers by this authorHideyuki Okano MD, PhD
Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
Search for more papers by this authorYoshikuni Mizuno MD, PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hideki Mochizuki MD, PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanSearch for more papers by this authorKenji Yoshimi PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorYong-Ri Ren MD
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorTatsunori Seki PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Department of Anatomy, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorMasanori Yamada PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorHideki Ooizumi MD
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorMasafumi Onodera MD, PhD
Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Tokyo, Japan
Search for more papers by this authorYuko Saito MD, PhD
Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
Search for more papers by this authorShigeo Murayama MD, PhD
Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
Search for more papers by this authorHideyuki Okano MD, PhD
Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
Search for more papers by this authorYoshikuni Mizuno MD, PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hideki Mochizuki MD, PhD
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanSearch for more papers by this authorAbstract
Recent studies of enhanced hippocampal neurogenesis by antidepressants suggest enhancement of neurogenesis is a potentially effective therapy in neurodegenerative diseases. In this study, we evaluated nigral neurogenesis in animals and autopsy brains including patients with Parkinson's disease (PD). First, proliferating cells in substantia nigra were labeled with retroviral transduction of green fluorescent protein, which is an efficient method to label neuronal stem cells. Subsequent differentiation of labeled cells was followed; many transduced cells became microglia, but no differentiation into tyrosine hydroxylase–positive neurons was detected at 4 weeks after injection, in both intact rodents and those treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Second, polysialic acid (PSA)–like immunoreactivity, indicative of newly differentiated neurons, was detected in the substantia nigra of rodent, primate, and human midbrains. A large number of PSA-positive cells were detected in the substantia nigra pars reticulata of some patients with PD. In rats and a macaque monkey, the dopamine-depleted hemispheres showed more PSA staining than the intact side. A small number of tyrosine hydroxylase–positive cells were PSA-positive. Our results suggest enhanced neural reconstruction in PD, which may be important in the design of new therapies against the progression of PD. Ann Neurol 2005
References
- 1 Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104–9110.
- 2 Banasr M, Hery M, Brezun JM, Daszuta A. Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus. Eur J Neurosci 2001; 14: 1417–1424.
- 3 Santarelli L, Saxe M, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805–809.
- 4 Armstrong RJ, Barker RA. Neurodegeneration: a failure of neuroregeneration? Lancet 2001; 358: 1174–1176.
- 5 Curtis MA, Penney EB, Pearson AG, et al. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc Natl Acad Sci U S A 2003; 100: 9023–9027.
- 6 Mikkonen M, Soininen H, Tapiola T, et al. Hippocampal plasticity in Alzheimer's disease: changes in highly polysialylated NCAM immunoreactivity in the hippocampal formation. Eur J Neurosci 1999; 11: 1754–1764.
- 7 Jin K, Peel AL, Mao XO, et al. Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci U S A 2004; 101: 343–347.
- 8 Hirsch EC, Hunot S, Faucheux B, et al. Dopaminergic neurons degenerate by apoptosis in Parkinson's disease. Mov Disord 1999; 14: 383–385.
- 9 Olanow CW, Goetz CG, Kordower JH, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 2003; 54: 403–414.
- 10 Kay JN, Blum M. Differential response of ventral midbrain and striatal progenitor cells to lesions of the nigrostriatal dopaminergic projection. Dev Neurosci 2000; 22: 56–67.
- 11 Lie DC, Dziewczapolski G, Willhoite AR, et al. The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 2002; 22: 6639–6649.
- 12 Zhao M, Momma S, Delfani K, et al. Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci U S A 2003; 100: 7925–7930.
- 13 Frielingsdorf H, Schwarz K, Brundin P, Mohapel P. No evidence for new dopaminergic neurons in the adult mammalian substantia nigra. Proc Natl Acad Sci U S A 2004; 101: 10177–10182.
- 14 Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 2002; 110: 429–441.
- 15 Zhu DY, Lau L, Liu SH, et al. Activation of cAMP-response-element-binding protein (CREB) after focal cerebral ischemia stimulates neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 2004; 101: 9453–9457.
- 16 Kawai T, Takagi N, Miyake-Takagi K, et al. Characterization of BrdU-positive neurons induced by transient global ischemia in adult hippocampus. J Cereb Blood Flow Metab 2004; 24: 548–555.
- 17 Rakic P. Adult neurogenesis in mammals: an identity crisis. J Neurosci 2002; 22: 614–618.
- 18 Gould E, Gross CG. Neurogenesis in adult mammals: some progress and problems. J Neurosci 2002; 22: 619–623.
- 19 Suzuki SO, Goldman JE. Multiple cell populations in the early postnatal subventricular zone take distinct migratory pathways: a dynamic study of glial and neuronal progenitor migration. J Neurosci 2003; 23: 4240–4250.
- 20 Kaneko S, Onodera M, Fujiki Y, et al. Simplified retroviral vector gcsap with murine stem cell virus long terminal repeat allows high and continued expression of enhanced green fluorescent protein by human hematopoietic progenitors engrafted in nonobese diabetic/severe combined immunodeficient mice. Hum Gene Ther 2001; 12: 35–44.
- 21 Suzuki A, Obi K, Urabe T, et al. Feasibility of ex vivo gene therapy for neurological disorders using the new retroviral vector GCDNsap packaged in the vesicular stomatitis virus G protein. J Neurochem 2002; 82: 953–960.
- 22 Yamada M, Onodera M, Mizuno Y, Mochizuki H. Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice. Neuroscience 2004; 124: 173–181.
- 23 Tanaka R, Yamashiro K, Mochizuki H, et al. Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector. Stroke 2004; 35: 1454–1459.
- 24 Seki T, Arai Y. Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat. J Neurosci 1993; 13: 2351–2358.
- 25 Fukuda S, Kato F, Tozuka Y, et al. Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus. J Neurosci 2003; 23: 9357–9366.
- 26 Furuya T, Hayakawa H, Yamada M, et al. Caspase-11 mediates inflammatory dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. J Neurosci 2004; 24: 1865–1872.
- 27 Przedborski S, Jackson-Lewis V, Naini AB, et al. The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 2001; 76: 1265–1274.
- 28 Altar CA, Heikkila RE, Manzino L, Marien MR. 1-Methyl-4-phenylpyridine (MPP+): regional dopamine neuron uptake, toxicity, and novel rotational behavior following dopamine receptor proliferation. Eur J Pharmacol 1986; 131: 199–209.
- 29 Imai H, Nakamura T, Endo K, Narabayashi H. Hemiparkinsonism in monkeys after unilateral caudate nucleus infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): behavior and histology. Brain Res 1988; 474: 327–332.
- 30 Mochizuki H, Imai H, Endo K, et al. Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. Neurosci Lett 1994; 168: 251–253.
- 31 Ito D, Imai Y, Ohsawa K, et al. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 1998; 57: 1–9.
- 32 Dawson MR, Levine JM, Reynolds R. NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J Neurosci Res 2000; 61: 471–479.
- 33 Cammer W, Zhang H. Localization of Pi class glutathione-S-transferase in the forebrains of neonatal and young rats: evidence for separation of astrocytic and oligodendrocytic lineages. J Comp Neurol 1992; 321: 40–45.
- 34 Yoshimi K, Iwata N, Takeda M, et al. Ischaemia-induced change in clathrin preceding delayed neuronal death. Neuroreport 1995; 6: 453–456.
- 35 Nomura T, Yabe T, Rosenthal ES, Krzan M, Schwartz JP. PSA-NCAM distinguishes reactive astrocytes in 6-OHDA-lesioned substantia nigra from those in the striatal terminal fields. J Neurosci Res 2000; 6: 588–596.
- 36 Kawano H, Ohyama K, Kawamura K, Nagatsu I. Migration of dopaminergic neurons in the embryonic mesencephalon of mice. Brain Res Dev Brain Res 1995; 86: 101–113.
- 37 Hokfelt-T, Martensson-R, Bjorklund-A, et al. Distributional maps of tyrosine-hydroxylase-immunoreactive neurons in the rat brain. Handbook of chemical neuroanatomy. Vol 2. New York: Elsevier, 1984: 277.
- 38 Alvarez-Buylla A, Garcia-Verdugo JM. Neurogenesis in adult subventricular zone. J Neurosci 2002; 22: 629–634.
- 39 Belachew S, Chittajallu R, Aguirre AA, et al. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol 2003; 161: 169–186.
- 40 Yokoyama A, Yang L, Itoh S, et al. Microglia, a potential source of neurons, astrocytes, and oligodendrocytes. Glia 2004; 45: 96–104.
- 41 Jackson-Lewis V, Jakowec M, Burke RE, Przedborski S. Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration 1995; 4: 257–269.
- 42 Ho A, Blum M. Induction of interleukin-1 associated with compensatory dopaminergic sprouting in the denervated striatum of young mice: model of aging and neurodegenerative disease. J Neurosci 1998; 18: 5614–5629.
- 43 Hoglinger GU, Rizk P, Muriel MP, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 2004; 7: 726–735.
- 44 Marek K, Jennings D, Seibyl J. Do dopamine agonists or levodopa modify Parkinson's disease progression? Eur J Neurol 2002; 9(suppl 3): 15–22.
- 45 Stocchi F, Olanow CW. Neuroprotection in Parkinson's disease: clinical trials. Ann Neurol 2003; 53(suppl 3): S87–S97.
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