Fibroblast growth factor 2 enhances striatal and nigral neurogenesis in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.
In response to injury, endogenous precursors in the adult brain can proliferate and generate new neurons, which may have the capacity to replace dysfunctional or dead cells. Although injury-induced neurogenesis has been demonstrated in animal models of stroke, Alzheimer's disease (AD) and Huntington's disease (HD), studies of Parkinson's disease (PD) have produced conflicting results. In this study, we investigated the ability of adult mice to generate new neurons in response to the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes selective degeneration of nigrostriatal dopamine neurons. MPTP lesions increased the incorporation of 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU), as well as the number of cells that co-expressed BrdU and the immature neuronal marker doublecortin (DCX), in two neuroproliferative regions-the subgranular zone of the dentate gyrus (DG) and the rostral subventricular zone (SVZ). BrdU-labeled, DCX-expressing cells were not found in the substantia nigra (SN) of MPTP-treated mice, where neuronal cell bodies are destroyed, but were present in increased numbers in the striatum, where SN neurons lost in PD normally project. Fibroblast growth factor-2 (FGF-2), which enhances neurogenesis in a mouse model of HD, also increased the number of BrdU/DCX-immunopositive cells in the SN of MPTP-treated mice. Thus, MPTP-induced brain injury increases striatal neurogenesis and, in combination with FGF-2 treatment, also stimulates neurogenesis in SN.
Peng
J
J
Buck Institute for Age Research, Novato, CA 94945, USA.
Xie
L
L
Jin
K
K
Greenberg
D A
DA
Andersen
J K
JK
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000089662:Doublecortin Protein; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D016222:Fibroblast Growth Factor 2