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

被引:49
作者
Chaturvedi, RK [1 ]
Shukla, S [1 ]
Seth, K [1 ]
Agrawal, AK [1 ]
机构
[1] Ind Toxicol Res Ctr, Div Dev Toxicol, Lucknow, Uttar Pradesh, India
关键词
D-amphetamine; dopamine; tyrosine hydroxylase; NGF; neurorescue;
D O I
10.1016/j.neulet.2005.12.042
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:44 / 49
页数:6
相关论文
共 27 条
[11]   GDNF PROTECTS NIGRAL DOPAMINE NEURONS AGAINST 6-HYDROXYDOPAMINE IN-VIVO [J].
KEARNS, CM ;
GASH, DM .
BRAIN RESEARCH, 1995, 672 (1-2) :104-111
[12]   Ectopic expression of the TrkA receptor in adult dopaminergic mesencephalic neurons promotes retrograde axonal NGF transport and NGF-dependent neuroprotection [J].
Melchior, B ;
Nerrière-Daguin, V ;
Laplaud, DA ;
Rémy, S ;
Wiertlewski, S ;
Neveu, I ;
Naveilhan, P ;
Meakin, SO ;
Brachet, P .
EXPERIMENTAL NEUROLOGY, 2003, 183 (02) :367-378
[13]   Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration [J].
Palfi, S ;
Leventhal, L ;
Chu, YP ;
Ma, SY ;
Emborg, M ;
Bakay, R ;
Déglon, N ;
Hantraye, P ;
Aebischer, P ;
Kordower, JH .
JOURNAL OF NEUROSCIENCE, 2002, 22 (12) :4942-4954
[14]  
Paxinos G, 1998, RAT BRAIN IN STEREOTAXIC COORDINATES, FOURTH ED., pix
[15]   Nerve growth factor levels in Parkinson disease and experimental parkinsonian rats [J].
Pedre, LL ;
Fuentes, NP ;
González, LA ;
McRae, A ;
Sánchez, TS ;
Lescano, LB ;
González, RM .
BRAIN RESEARCH, 2002, 952 (01) :122-127
[16]   Adult brain neurogenesis and pathology [J].
Rougier, A ;
Auvergne, R .
NEUROCHIRURGIE, 2004, 50 (01) :33-41
[17]   Nerve growth factor protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a phosphatidylinositol 3-kinase-dependent manner [J].
Salinas, M ;
Diaz, R ;
Abraham, NG ;
de Galarreta, CMR ;
Cuadrado, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (16) :13898-13904
[18]   Caspase inhibition reduces apoptosis and increases survival of nigral transplants [J].
Schierle, GS ;
Hansson, O ;
Leist, M ;
Nicotera, P ;
Widner, H ;
Brundin, P .
NATURE MEDICINE, 1999, 5 (01) :97-100
[19]  
Shimoke K, 2001, J NEUROSCI RES, V63, P402, DOI 10.1002/1097-4547(20010301)63:5<402::AID-JNR1035>3.0.CO
[20]  
2-F