Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism
Identifieur interne : 001F99 ( Main/Exploration ); précédent : 001F98; suivant : 002000Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism
Auteurs : Caixin Su [Canada] ; Nada Elfeki [Canada] ; Patrizia Ballerini [Italie] ; Iolanda D'Alimonte [Italie] ; Christian Bau [Canada] ; Renata Ciccarelli [Italie] ; Francesco Caciagli [Italie] ; Joseph Gabriele [Canada] ; Shucui Jiang [Canada]Source :
- Journal of Neuroscience Research [ 0360-4012 ] ; 2009-02-15.
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Abstract
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.
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DOI: 10.1002/jnr.21883
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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.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Italie</li></country><region><li>Ontario</li></region><settlement><li>Hamilton (Ontario)</li></settlement><orgName><li>Université McMaster</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Su, Caixin" sort="Su, Caixin" uniqKey="Su C" first="Caixin" last="Su">Caixin Su</name></region><name sortKey="Bau, Christian" sort="Bau, Christian" uniqKey="Bau C" first="Christian" last="Bau">Christian Bau</name><name sortKey="Elfeki, Nada" sort="Elfeki, Nada" uniqKey="Elfeki N" first="Nada" last="Elfeki">Nada Elfeki</name><name sortKey="Gabriele, Joseph" sort="Gabriele, Joseph" uniqKey="Gabriele J" first="Joseph" last="Gabriele">Joseph Gabriele</name><name sortKey="Jiang, Shucui" sort="Jiang, Shucui" uniqKey="Jiang S" first="Shucui" last="Jiang">Shucui Jiang</name><name sortKey="Jiang, Shucui" sort="Jiang, Shucui" uniqKey="Jiang S" first="Shucui" last="Jiang">Shucui Jiang</name></country><country name="Italie"><noRegion><name sortKey="Ballerini, Patrizia" sort="Ballerini, Patrizia" uniqKey="Ballerini P" first="Patrizia" last="Ballerini">Patrizia Ballerini</name></noRegion><name sortKey="Caciagli, Francesco" sort="Caciagli, Francesco" uniqKey="Caciagli F" first="Francesco" last="Caciagli">Francesco Caciagli</name><name sortKey="Ciccarelli, Renata" sort="Ciccarelli, Renata" uniqKey="Ciccarelli R" first="Renata" last="Ciccarelli">Renata Ciccarelli</name><name sortKey="D Alimonte, Iolanda" sort="D Alimonte, Iolanda" uniqKey="D Alimonte I" first="Iolanda" last="D'Alimonte">Iolanda D'Alimonte</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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