Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging

Date, Isao; Yoshimoto, Yusuke; Imaoka, Takashi; Miyoshi, Yasuyuki; Gohda, Yuji; Furuta, Tomohisa; Asari, Shoji; Ohmoto, Takashi

doi:10.1016/0006-8993(93)90312-b

Cited by 58 publications

(23 citation statements)

References 28 publications

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“…Basic FGF has previously been reported to have beneficial effects on the survival of dopaminergic neurons in vitro and in vivo (Otto and Unsicker, 1990;Date et al, 1993;Chadi et al, 1993). This may be an indirect effect, since when astrocytes are activated with bFGF, they produce a factor or factors which strongly promotes the differentiation of mid-brain dopaminergic neurons in culture (Gaul and Lübbert, 1992).…”

Section: Discussionmentioning

confidence: 97%

L1 neural cell adhesion molecule is a survival factor for fetal dopaminergic neurons

1998

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Cell adhesion molecules play a central role in neural development and are also critically involved in axonal regeneration and synaptic plasticity in the adult nervous system. We investigated whether the neural cell adhesion molecule L1 was capable of stimulating survival and differentiation in the mid-brain dopaminergic neurons which degenerate in Parkinson's disease. Monoclonal L1 antibodies, known to enhance neurite outgrowth, were substrate-coated or added at the time of plating to medium of cultures containing mid-brain dopaminergic neurons from 14-day-old fetal rats. Tritiated dopamine uptake per well and the number of tyrosine hydroxylase-immunopositive neurons increased in a dose-dependent manner with increasing concentrations of L1 antibody, suggesting that L1 acts directly or indirectly as a growth factor for dopaminergic neurons. A monoclonal L1 antibody not enhancing neurite outgrowth was ineffective. The growth-promoting effects of L1 antibodies on dopaminergic neurons in culture did not appear to be mediated by the cAMP-activated protein kinase A pathway, since combined treatment with a phosphodiesterase inhibitor had only additive effects on the L1-induced increase of dopamine uptake, and in addition, antibodies against L1 failed to protect cultures of dopaminergic neurons against the neurotoxin MPP+, whereas pretreatment with forskolin and phosphodiesterase type-IV inhibitors was strongly protective.

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Section: Discussionmentioning

confidence: 97%

L1 neural cell adhesion molecule is a survival factor for fetal dopaminergic neurons

1998

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“…administration of an FGF-2-expressing herpes simplex virus amplicon vector (Yoshimura et al, 2001). In fact, FGF-2 is depleted from the SN in PD (Tooyama et al, 1993) and treatment with FGF-2 enhances histological and biochemical recovery from MPTP lesioning in mice (Date et al, 1993). Additional studies involving more prolonged monitoring and tests of neuronal function are required to evaluate these possibilities.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

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

Peng¹,

Xie²,

Jin³

et al. 2008

Neuroscience

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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 regionsthe subgranular zone of the dentate gyrus (DG) and the rostral subventricular zone (SVZ). BrdUlabeled, 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.Keywords fibroblast growth factor; Parkinson's disease; proliferation; progenitor; striatum; substantia nigra Parkinson's disease (PD) is the second most frequently occurring neurodegenerative disorder after Alzheimer's disease (AD), affecting about 1% of the population over the age of 50 in North America (Forno, 1996;Lang and Lozano, 1998). Despite progress in understanding molecular mechanisms in PD, fully effective treatment remains elusive. One new potential strategy for replacing midbrain dopaminergic neurons in PD is based on endogenous neuroproliferation in the rostral subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (DG). Neurogenesis is increased in these regions in certain neurological disorders including AD (Jin et al., 2004b), Huntington's disease (HD) (Curtis et al., 2003) and stroke (Jin et al., 2001). Furthermore, endogenous neurogenesis in neuroproliferative zones of the adult brain is enhanced by administration or overexpression of growth factors, including brain-derived neurotrophic factor (BDNF) (Pencea et al., 2001), epidermal growth factor (EGF) (Craig et al., 1996), fibroblast growth factor 2 (FGF-2) (Kuhn *Corresponding author. Tel: +1-415-209-2070; fax: +1-415-209-2231. jandersen@buckinstitute.org (J. K. Andersen). NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 May 5. , 1997;Wagner et al., 1999), heparin-binding EGF (HB-EGF) (Jin et al., 2002b), stem cell factor (SCF) (Jin et al., 2002a) and vasc...

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“…With regard to the in vivo situation, FGF-2 has been efficiently used in different treatment protocols in mouse and rat PD models. Intrastriatal infusions of FGF-2 induced recovery of striatal DA fibers and DA content in the mouse 1-methyl-1,2,3,6-tetrahydo-pyridine (MPTP)-model and increased the protection of the neurotoxicityinduced lesioned nigrostriatal DA system (Date et al, 1993). In addition, survival of grafted DA neurons was also enhanced after repeated intracerebral infusions or pretreatment of transplanted cells with FGF-2 (Mayer et al, 1993b).…”

Section: Introductionmentioning

confidence: 97%

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

Cesnulevicius²,

et al. 2007

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Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (ϩ/Ϫ) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2 Ϫ/Ϫ and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2 Ϫ/Ϫ mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.

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Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging

Cited by 58 publications

References 28 publications

L1 neural cell adhesion molecule is a survival factor for fetal dopaminergic neurons

L1 neural cell adhesion molecule is a survival factor for fetal dopaminergic neurons

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

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

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