Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson's disease

doi:10.1016/j.neulet.2005.12.042

Neuroscience Letters

Volume 398, Issues 1–2, 1 May 2006, Pages 44-49

https://doi.org/10.1016/j.neulet.2005.12.042 Get rights and content

Abstract

In the present study, an attempt has been made to explore the neuroprotective and neurorescue effects of nerve growth factor (NGF) on grafted cells and on host nigral dopaminergic neurons, respectively. NGF was co-transplanted with fetal ventral mesencephalic cells (VMC) in the striatum of 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). In the other groups fetal VMC and NGF were transplanted alone. Twelve weeks post-transplantation, a significant restoration was observed in d-amphetamine induced rotations (stereotypy), spontaneous locomotor activity, striatal and nigral dopamine (DA) and 3,4-dihydroxy-phenyl acetic acid (DOPAC) levels in co-transplanted rats as compared to VMC alone transplanted rats. Higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons and significantly increased fiber outgrowth from graft was evident in co-transplanted rats as compared to VMC alone transplanted rats. Further, a significant increase was also observed in substantia nigra TH-ir neurons count in co-transplanted rats, exhibiting a potential neuroprotective and neurorescue effects of NGF on nigrostriatal dopaminergic neurons. The results suggest that NGF at the time of transplantation exhibits neuroprotective effect on transplanted VMC as well as neurorescue effect on remaining host nigral dopaminergic neurons, leading to better functional restoration.

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Acknowledgements

R.K.C. and S.S. are SRF in CSIR, New Delhi. K.S. is WOS in DST, New Delhi. Financial support of DST, New Delhi is gratefully acknowledged (ITRC MS communication No. 2321).

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Citation Excerpt :
The findings that neurotrophic factors support neuronal survival and differentiation were rapidly implemented in strategies to improve the outcome of transplantations. Indeed, pre- or co-treatment of midbrain transplants with neurotrophin-4/5 (NT4/5), brain derived neurotrophic factor or glial cell line-derived neurotrophic factor (GDNF) have been reported to improve functional recovery, to elevate numbers of dopaminergic neurons in the grafts and to increase the number of graft derived fibres growing into the host brain (Andereggen et al., 2009; Chaturvedi et al., 2006; Espejo et al., 2000; Haque et al., 1996; Mehta et al., 1998). In line with these observations, treatment of foetal midbrain cultures with either NT4/5 or GDNF led to an enhanced survival of dopaminergic neurons and GDNF promoted their morphological complexity (Lin et al., 1993; Meyer et al., 2001; Widmer et al., 2000).
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Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson's disease

Abstract

Section snippets

Acknowledgements

J. Chem. Neuroanat.

Neurobiol. Dis.

J. Biol. Chem.

Brain Res.

Int. J. Dev. Neurosci.

Exp. Neurol.

Parkinson. Relat. Disord.

Brain Res.

Exp. Neurol.

Brain Res.

Brain Res.

Exp. Neurol.