Antiparkinsonian trophic action of glial cell line-derived neurotrophic factor and transforming growth factor β1 is enhanced after co-infusion in rats

Gonzalez-Aparicio, R.; Flores, Juan; Fernández-Espejo, Emilio

doi:10.1016/j.expneurol.2010.08.016

Cited by 27 publications

(14 citation statements)

References 50 publications

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“…TGF-β regulates the availability of the glycosyl phosphatidylinositol GPI-anchored GFRα1 by promoting the recruitment of the receptor to the plasma membrane (Peterziel et al, 2007). Also, additive effects of GDNF with TGF-β1, given by osmotic minipumps to the dorsal striatum (Gonzalez-Aparicio et al, 2010), and of MANF with CDNF, given as a special lentiviral gene construct to the SN (Cordero-Llana et al, 2015), were reported in the 6-OHDA model of PD in rats. The latter finding suggests that although MANF and CDNF belong to the same protein family, even these proteins may differ in their mode of action.…”

Section: Discussionmentioning

confidence: 99%

Evidence for an Additive Neurorestorative Effect of Simultaneously Administered CDNF and GDNF in Hemiparkinsonian Rats: Implications for Different Mechanism of Action

Voutilainen

Lorenzo

Stepanova

et al. 2017

eNeuro

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Parkinson’s disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD. Here, we report an additive neurorestorative effect of coadministration of CDNF and GDNF in the unilateral 6-hydroxydopamine (6-OHDA) lesion model of PD in rats. NTFs were given into the striatum four weeks after unilateral intrastriatal injection of 6-OHDA (20 µg). Amphetamine-induced (2.5 mg/kg, i.p.) rotational behavior was measured every two weeks. Number of tyrosine hydroxylase (TH)-positive cells from SN pars compacta (SNpc) and density of TH-positive fibers in the striatum were analyzed at 12 weeks after lesion. CDNF and GDNF alone restored the DAergic function, and one specific dose combination had an additive effect: CDNF (2.5µg) and GDNF (1µg) coadministration led to a stronger trophic effect relative to either of the single treatments alone. The additive effect may indicate different mechanism of action for the NTFs. Indeed, both NTFs activated the survival promoting PI3 kinase (PI3K)-Akt signaling pathway, but only CDNF decreased the expression level of tested endoplasmatic reticulum (ER) stress markers ATF6, glucose-regulated protein 78 (GRP78), and phosphorylation of eukaryotic initiation factor 2α subunit (eIF2α).

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Section: Discussionmentioning

confidence: 99%

Evidence for an Additive Neurorestorative Effect of Simultaneously Administered CDNF and GDNF in Hemiparkinsonian Rats: Implications for Different Mechanism of Action

Voutilainen

Lorenzo

Stepanova

et al. 2017

eNeuro

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show abstract

“…These results identify that microglia are a required target for TGF-b1 neuroprotection. In several in vivo studies, TGF-b1 has been shown to have a synergic protective effect with glial cellderived neurotrophic factor (GDNF) in PD animal models (Gonzalez-Aparicio et al, 2010;Schober et al, 2007). However, Sánchez-Capelo et al (2003) reported that increase in TGF-b1 levels aggravates the Parkinsonian status of MPTP mice and may therefore be a risk factor for the development of PD.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-β1 acts via TβR-I on microglia to protect against MPP+-induced dopaminergic neuronal loss

Chen

Huang

et al. 2016

Brain, Behavior, and Immunity

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“…Apomorphine-induced rotational behavior is a good indicator of extensive lesions of the nigrostriatal pathway [20], and is considered a valuable behavioral index to test novel drugs against PD [23], [24]. At ten days following unilateral lesion of the nigrostriatal pathway, motor asymmetry was monitored over 15 min after subcutaneous injection of apomorphine (0.5 mg/kg diluted in 0.9% saline).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Activity of Peripherally Administered Liver Growth Factor in a Rat Model of Parkinson’s Disease

et al. 2013

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Liver growth factor (LGF) is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson’s disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat) for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson’s disease.

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Antiparkinsonian trophic action of glial cell line-derived neurotrophic factor and transforming growth factor β1 is enhanced after co-infusion in rats

Cited by 27 publications

References 50 publications

Evidence for an Additive Neurorestorative Effect of Simultaneously Administered CDNF and GDNF in Hemiparkinsonian Rats: Implications for Different Mechanism of Action

Evidence for an Additive Neurorestorative Effect of Simultaneously Administered CDNF and GDNF in Hemiparkinsonian Rats: Implications for Different Mechanism of Action

Transforming growth factor-β1 acts via TβR-I on microglia to protect against MPP+-induced dopaminergic neuronal loss

Neuroprotective Activity of Peripherally Administered Liver Growth Factor in a Rat Model of Parkinson’s Disease

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