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Increased progenitor cell proliferation and astrogenesis in the partial progressive 6-hydroxydopamine model of Parkinson's disease.

Abstract

The existence of endogenous progenitor cells in the adult mammalian brain presents an exciting and attractive alternative to existing therapeutic options for treating neurodegenerative diseases such as Parkinson's disease (PD). However, prior to designing endogenous cell therapies, the effect of PD neuropathology on endogenous progenitor cell proliferation and their neurogenic potential must be investigated. This study examined the effect of dopaminergic cell loss on the proliferation and differentiation of subventricular zone- (SVZ) and midbrain-derived progenitor cells in the adult rodent brain, using the partial progressive 6-hydroxydopamine (6-OHDA) lesion model of PD. Cell proliferation and differentiation were assessed with 5-bromo-2'-deoxyuridine (BrdU) labeling and immunohistochemistry for cell type-specific markers. Tyrosine hydroxylase immunohistochemistry demonstrated a complete loss of nigrostriatal projections in the striatum and a subsequent progressive loss of dopamine (DA) cells in the SN. Quantification indicated that 6-OHDA lesion-induced cell degeneration produced a significant increase in BrdU immunoreactivity in the SVZ, ipsilateral to the lesioned hemisphere from 3 to 21 days post-lesion, compared with sham-lesioned animals. Similarly, in the striatum we observed a significant increase in the total number of BrdU positive cells in 6-OHDA-lesioned animals at all time points examined. More importantly, a significant increase in midbrain-derived BrdU positive cells was demonstrated in 6-OHDA-lesioned animals 28 days post-lesion. While we did not detect neurogenesis, BrdU labeled cells co-expressing the astrocytic marker glial fibrillary acidic protein (GFAP) were widely distributed throughout the 6-OHDA-lesioned striatum at all time points. In contrast, BrdU-labeled cells in the SN of 6-OHDA-lesioned animals did not co-express neural markers. These results demonstrate that DA-ergic neurodegeneration in the partial progressive 6-OHDA-lesioned rat brain increases SVZ- and midbrain-derived progenitor cell proliferation. While, newborn striatal progenitors undergo robust astrogenesis, newborn midbrain-derived progenitors remain in an undifferentiated state suggesting local environments differentially regulate endogenous progenitor cell populations in PD.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.

    ,

    Source

    Neuroscience 151:4 2008 Feb 19 pg 1142-53

    MeSH

    Adrenergic Agents
    Adult Stem Cells
    Analysis of Variance
    Animals
    Astrocytes
    Bromodeoxyuridine
    Cell Differentiation
    Cell Proliferation
    Corpus Striatum
    Disease Models, Animal
    Glial Fibrillary Acidic Protein
    Male
    Oxidopamine
    Parkinson Disease
    Rats
    Rats, Wistar
    Substantia Nigra
    Time Factors
    Tyrosine 3-Monooxygenase

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18201835

    Citation

    Aponso, P M., et al. "Increased Progenitor Cell Proliferation and Astrogenesis in the Partial Progressive 6-hydroxydopamine Model of Parkinson's Disease." Neuroscience, vol. 151, no. 4, 2008, pp. 1142-53.
    Aponso PM, Faull RL, Connor B. Increased progenitor cell proliferation and astrogenesis in the partial progressive 6-hydroxydopamine model of Parkinson's disease. Neuroscience. 2008;151(4):1142-53.
    Aponso, P. M., Faull, R. L., & Connor, B. (2008). Increased progenitor cell proliferation and astrogenesis in the partial progressive 6-hydroxydopamine model of Parkinson's disease. Neuroscience, 151(4), pp. 1142-53. doi:10.1016/j.neuroscience.2007.11.036.
    Aponso PM, Faull RL, Connor B. Increased Progenitor Cell Proliferation and Astrogenesis in the Partial Progressive 6-hydroxydopamine Model of Parkinson's Disease. Neuroscience. 2008 Feb 19;151(4):1142-53. PubMed PMID: 18201835.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Increased progenitor cell proliferation and astrogenesis in the partial progressive 6-hydroxydopamine model of Parkinson's disease. AU - Aponso,P M, AU - Faull,R L M, AU - Connor,B, Y1 - 2007/12/04/ PY - 2007/10/14/received PY - 2007/11/20/revised PY - 2007/11/28/accepted PY - 2008/1/19/pubmed PY - 2008/6/13/medline PY - 2008/1/19/entrez SP - 1142 EP - 53 JF - Neuroscience JO - Neuroscience VL - 151 IS - 4 N2 - The existence of endogenous progenitor cells in the adult mammalian brain presents an exciting and attractive alternative to existing therapeutic options for treating neurodegenerative diseases such as Parkinson's disease (PD). However, prior to designing endogenous cell therapies, the effect of PD neuropathology on endogenous progenitor cell proliferation and their neurogenic potential must be investigated. This study examined the effect of dopaminergic cell loss on the proliferation and differentiation of subventricular zone- (SVZ) and midbrain-derived progenitor cells in the adult rodent brain, using the partial progressive 6-hydroxydopamine (6-OHDA) lesion model of PD. Cell proliferation and differentiation were assessed with 5-bromo-2'-deoxyuridine (BrdU) labeling and immunohistochemistry for cell type-specific markers. Tyrosine hydroxylase immunohistochemistry demonstrated a complete loss of nigrostriatal projections in the striatum and a subsequent progressive loss of dopamine (DA) cells in the SN. Quantification indicated that 6-OHDA lesion-induced cell degeneration produced a significant increase in BrdU immunoreactivity in the SVZ, ipsilateral to the lesioned hemisphere from 3 to 21 days post-lesion, compared with sham-lesioned animals. Similarly, in the striatum we observed a significant increase in the total number of BrdU positive cells in 6-OHDA-lesioned animals at all time points examined. More importantly, a significant increase in midbrain-derived BrdU positive cells was demonstrated in 6-OHDA-lesioned animals 28 days post-lesion. While we did not detect neurogenesis, BrdU labeled cells co-expressing the astrocytic marker glial fibrillary acidic protein (GFAP) were widely distributed throughout the 6-OHDA-lesioned striatum at all time points. In contrast, BrdU-labeled cells in the SN of 6-OHDA-lesioned animals did not co-express neural markers. These results demonstrate that DA-ergic neurodegeneration in the partial progressive 6-OHDA-lesioned rat brain increases SVZ- and midbrain-derived progenitor cell proliferation. While, newborn striatal progenitors undergo robust astrogenesis, newborn midbrain-derived progenitors remain in an undifferentiated state suggesting local environments differentially regulate endogenous progenitor cell populations in PD. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18201835/Increased_progenitor_cell_proliferation_and_astrogenesis_in_the_partial_progressive_6_hydroxydopamine_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)01534-5 DB - PRIME DP - Unbound Medicine ER -