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Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism
Author(s) -
Su Caixin,
Elfeki Nada,
Ballerini Patrizia,
D'Alimonte Iolanda,
Bau Christian,
Ciccarelli Renata,
Caciagli Francesco,
Gabriele Joseph,
Jiang Shucui
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21883
Subject(s) - subventricular zone , substantia nigra , pars compacta , neurogenesis , tyrosine hydroxylase , neural stem cell , microbiology and biotechnology , dopaminergic , progenitor cell , neuroregeneration , doublecortin , biology , stem cell , chemistry , medicine , endocrinology , dopamine , hippocampus , regeneration (biology) , dentate gyrus
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) caused by an abnormal rate of apoptosis. Endogenous stem cells in the adult mammalian brain indicate an innate potential for regeneration and possible resource for neuroregeneration in PD. We previously showed that guanosine prevents apoptosis even when administered 48 hr after the toxin 1‐methyl‐4‐phenylpyridinium (MPP + ). Here, we induced parkinsonism in rats with a proteasome inhibitor. Guanosine treatment reduced apoptosis, increased tyrosine hydroxylase–positive dopaminergic neurons and expression of tyrosine hydroxylase in the SNc, increased cellular proliferation in the SNc and subventricular zone, and ameliorated symptoms. Proliferating cells in the subventricular zone were nestin‐positive adult neural progenitor/stem cells. Fibroblast growth factor‐2‐expressing cells were also increased by guanosine. Thus, guanosine protected cells from apoptosis and stimulated “intrinsic” adult progenitor/stem cells to become dopaminergic neurons in rats with proteasome inhibitor–induced PD. The cellular/molecular mechanisms underlying these effects may open new avenues for development of novel therapeutics for PD. © 2008 Wiley‐Liss, Inc.