Differential expression of the cell line-derived neurotrophic factor (GDNF) receptor GFRα1 in heterozygous Gfrα1 null-mutant mice after stroke

Sarabi, Arezou; Chang, Chen-Fu; Wang, Y.; Tomac, Andreas C.; Hoffer, Barry J.; Morales, Marisela

doi:10.1016/s0304-3940(03)00195-2

Cited by 16 publications

(13 citation statements)

References 24 publications

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“…Indeed, reports have demonstrated that IL-6 and GDNF receptor expression was increased in the contralateral hemisphere in an ischemic model (Suzuki et al, 1999;Sarabi et al, 2003). These altered gene expressions of growth factors in the contralateral region might be due to an altered crerbral blood flow in remote regions or a reactive response to crerbral ischemia, which might lead to protection against ischemic brain damage.…”

Section: Discussionmentioning

confidence: 97%

Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model

Wakabayashi

Nagai

Sheikh

et al. 2009

J of Neuroscience Research

220

158

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Previous studies have suggested that intravenous transplantation of mesenchymal stem cells (MSCs) in rat ischemia models reduces ischemia-induced brain damage. Here, we analyzed the expression of neurotrophic factors in transplanted human MSCs and host brain tissue in rat middle cerebral artery occlusion (MCAO) ischemia model. At 1 day after transient MCAO, 3 x 10(6) immortalized human MSC line (B10) cells or PBS was intravenously transplanted. Behavioral tests, infarction volume, and B10 cell migration were investigated at 1, 3, 7, and 14 days after MCAO. The expression of endogenous (rat origin) and exogenous (human origin) neurotrophic factors and cytokines was evaluated by quantitative real-time RT-PCR and Western blot analysis. Compared with PBS controls, rats receiving MSC transplantation showed improved functional recovery and reduced brain infarction volume at 7 and 14 days after MCAO. In MSC-transplanted brain, among many neurotrophic factors, only human insulin-like growth factor 1 (IGF-1) was detected in the core and ischemic border zone at 3 days after MCAO, whereas host cells expressed markedly higher neurotrophic factors (rat origin) than control rats, especially vascular endothelial growth factor (VEGF) at 3 days and epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) at 7 days after MCAO. Intravenously transplanted human MSCs induced functional improvement, reduced infarct volume, and neuroprotection in ischemic rats, possibly by providing IGF-1 and inducing VEGF, EGF, and bFGF neurotrophic factors in host brain.

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Section: Discussionmentioning

confidence: 97%

Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model

Wakabayashi

Nagai

Sheikh

et al. 2009

J of Neuroscience Research

220

158

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“…Changes in the regional and cellular expression of different trophic molecules, belonging either to the GDNF or to the neurotrophin family, and relevant receptors have been previously reported in the developing and adult rat nervous system (Maisonpierre et al, 1990; Treanor et al, 1996; Trupp et al, 1996; Buj‐Bello et al, 1997; Molliver et al, 1997; Nosrat et al, 1997; Sanicola et al, 1997; Suvanto et al, 1997; Widenfalk et al, 1997; Lenhard and Suter‐Crazzolara, 1998; Masure et al, 1998, 1999; Naveilhan et al, 1998; Worby et al, 1998; Yu et al, 1998; Åkerud et al, 1999; Burazin and Gundlach, 1999; Baudet et al, 2000; Airaksinen and Saarma, 2002). From a clinical perspective, it is interesting that the GDNF family ligands and receptors have been shown to undergo dynamic and differential changes in their expression following epileptic seizures induced in different experimental models (Trupp et al, 1997; Reeben et al, 1998; Kokaia et al, 1999; Chen et al, 2001) and forebrain ischemia (Kokaia et al, 1999; Ardvinsson et al, 2001; Miyazaki et al, 2001, 2002; Sarabi et al, 2001, 2003), indicating that the regulation of endogenous GDNF family signalling mechanisms may be critical for the determination of neuronal fate after brain insults, and that the structural changes and/or functional reorganization that occur in adult brain in the post‐insult period may depend upon the adaptive response of these molecules. Indeed, it has been shown that the intraventricular infusion of GDNF prevents kindling‐induced increases of the hilar area and sprouting of the mossy fibres in the rat (Li et al, 2000) and inhibits kainate‐mediated seizures (Martin et al, 1995) and that GDNF and ART prevent excitotoxic‐induced hippocampal neuronal loss (Bonde et al, 2000; Cheng et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Ret, GFRalpha‐1, GFRalpha‐2 and GFRalpha‐3 receptors in the human hippocampus and fascia dentata

Serra

Quartu²,

Mascia³

et al. 2005

Intl J of Devlp Neuroscience

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The immunohistochemical occurrence and localization of the receptor components of the glial cell line-derived neurotrophic factor (GDNF) family ligands, the Ret receptor tyrosine kinase and GDNF family receptor (GFR) alpha-1 to -3, is described in the human post-mortem hippocampal formation at pre- and full-term newborn, and adult age. Two different antibodies for each of the four-receptor molecules were used. Western blot analysis indicates that the availability of GFRalpha receptor proteins may vary with age and post-mortem delay. The immunohistochemical detectability of GFRalpha-1, GFRalpha-2, GFRalpha-3 and Ret receptor molecules is shown in the rat up to 72 h post-mortem. In the human specimens, labelled neuronal perikarya were detectable for each receptor protein at all examined ages, with prevalent localization in the pyramidal layer of the Ammon's horn and hilus and granular layer of the fascia dentata. In the adult subjects, abundant punctate-like structures were also present. Labelled glial elements were identifiable. Comparison of the pattern of immunoreactive elements among young and adult subjects suggests that the intracellular distribution of the GDNF family ligands may vary between pre- and perinatal life and adult age. The results obtained suggest the involvement of the Ret and GFRalpha receptors signalling in processes subserving both the organization of this cortical region during development and the functional activity and maintenance of the mature hippocampal neurons.

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“…The GFRα‐1 +/− mice were created by replacing the first coding exon of the murine GFRα‐1 gene with a phosphoglycerate kinase (pgk) neo‐resistance expression cassette in reverse orientation to GFRα‐1 mRNA transcription, as described earlier (Tomac et al. , 2000; Sarabi et al. , 2003).…”

Section: Methodsmentioning

confidence: 97%

The nigrostriatal dopamine system of aging GFRα‐1 heterozygous mice: neurochemistry, morphology and behavior

Zaman

Boger

Granholm

et al. 2008

Eur J of Neuroscience

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Given the established importance of glial cell line-derived neurotrophic factor (GDNF) in maintaining dopaminergic neurotransmitter systems, the nigrostriatal system and associated behaviors of mice with genetic reduction of its high-affinity receptor, GDNF receptor (GFR)α-1 (GFRα-1 +/− ), were compared with wild-type controls. Motor activity and the stimulatory effects of a dopamine (DA) D1 receptor agonist (SKF 82958) were assessed longitudinally at 8 and 18 months of age. Monoamine concentrations and dopaminergic nerve terminals in the striatum and the number of dopaminergic neurons in the substantia nigra (SN) were assessed. The results support the importance of GFRα-1 in maintaining normal function of the nigrostriatal dopaminergic system, with deficits being observed for GFRα-1 +/− mice at both ages. Motor activity was lower and the stimulatory effects of the DA agonist were enhanced for the older GFRα-1 +/− mice. DA in the striatum was reduced in the GFRα-1 +/− mice at both ages, and tyrosine hydroxylase-positive cell numbers in the SN were reduced most substantially in the older GFRα-1 +/− mice. The combined behavioral, pharmacological probe, neurochemical and morphological measures provide evidence of abnormalities in GFRα-1 +/− mice that are indicative of an exacerbated aging-related decline in dopaminergic system function. The noted deficiencies, in turn, suggest that GFRα-1 is necessary for GDNF to maintain normal function of the nigrostriatal dopaminergic system. Although the precise mechanism(s) for the aging-related changes in the dopaminergic system remain to be established, the present study clearly establishes that genetic reductions in GFRα-1 can contribute to the degenerative changes observed in this system during the aging process.

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Differential expression of the cell line-derived neurotrophic factor (GDNF) receptor GFRα1 in heterozygous Gfrα1 null-mutant mice after stroke

Cited by 16 publications

References 24 publications

Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model

Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model

Ret, GFRalpha‐1, GFRalpha‐2 and GFRalpha‐3 receptors in the human hippocampus and fascia dentata

The nigrostriatal dopamine system of aging GFRα‐1 heterozygous mice: neurochemistry, morphology and behavior

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