Effects of nerve and fibroblast growth factors on the production of nitric oxide in experimental model of Huntington's disease

Maksimovic, D Ivana; Jovanovic, D Marina; Malicevic, Zivorad; Čolić, Miodrag; Ninković, Milica

doi:10.2298/vsp0202119m

Cited by 7 publications

(2 citation statements)

References 20 publications

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“…FGF-2 is expressed in substantia nigra, striatum, and globus pallidus of human brain, and FGF receptor expression is increased in HD (36). In the quinolinic acid model of HD in rats, FGF-2 attenuates changes in cytochrome c oxidase (37) and nitric oxide synthase (24) activity, but there is little other prior evidence to connect FGF-2 with HD. The mechanisms through which FGF-2 produced neuroprotection in our HD transgenic R6͞2 mice may relate to the Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's disease

Jin

LaFevre-Bernt

Sun

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

186

121

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There is no satisfactory treatment for Huntington's disease (HD), a hereditary neurodegenerative disorder that produces chorea, dementia, and death. One potential treatment strategy involves the replacement of dead neurons by stimulating the proliferation of endogenous neuronal precursors (neurogenesis) and their migration into damaged regions of the brain. Because growth factors are neuroprotective in some settings and can also stimulate neurogenesis, we treated HD transgenic R6͞2 mice from 8 weeks of age until death by s.c. administration of FGF-2. FGF-2 increased the number of proliferating cells in the subventricular zone by Ϸ30% in wild-type mice, and by Ϸ150% in HD transgenic R6͞2 mice. FGF-2 also induced the recruitment of new neurons from the subventricular zone into the neostriatum and cerebral cortex of HD transgenic R6͞2 mice. In the striatum, these neurons were DARPP-32-expressing medium spiny neurons, consistent with the phenotype of neurons lost in HD. FGF-2 was neuroprotective as well, because it blocked cell death induced by mutant expanded Htt in primary striatal cultures. FGF-2 also reduced polyglutamine aggregates, improved motor performance, and extended lifespan by Ϸ20%. We conclude that FGF-2 improves neurological deficits and longevity in a transgenic mouse model of HD, and that its neuroprotective and neuroproliferative effects may contribute to this improvement.trophic factor ͉ polyglutamine

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Section: Discussionmentioning

confidence: 99%

FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's disease

Jin

LaFevre-Bernt

Sun

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

186

121

View full text Add to dashboard Cite

show abstract

“…Research suggests that the administration of antioxidant molecules blocks, reverses and prevents deterioration and molecular changes in both chemically-induced and transgenic animal models [22,23]. Studies using experimental HD models have shown that treatment with NGF lowers nitrotyrosine levels, indicating that NGF exerts a neuroprotective effect on striatum neurons [24,25]. Additionally, Cao et al have highlighted the therapeutic potential of nerve growth factor, noting that NGF administration causes a reduction in oxidative damage and enhances the capacity for cell proliferation and ROS scavenging [26].…”

Section: Discussionmentioning

confidence: 99%