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000137908 0247_ $$2doi$$a10.1111/jnc.13026
000137908 0247_ $$2pmid$$apmid:25581060
000137908 0247_ $$2ISSN$$a0022-3042
000137908 0247_ $$2ISSN$$a1471-4159
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000137908 037__ $$aDZNE-2020-04230
000137908 041__ $$aEnglish
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000137908 1001_ $$0P:(DE-HGF)0$$aDepboylu, Candan$$b0$$eCorresponding author
000137908 245__ $$aSystemically administered neuregulin-1β1 rescues nigral dopaminergic neurons via the ErbB4 receptor tyrosine kinase in MPTP mouse models of Parkinson's disease.
000137908 260__ $$aOxford$$bWiley-Blackwell$$c2015
000137908 264_1 $$2Crossref$$3online$$bWiley$$c2015-01-26
000137908 264_1 $$2Crossref$$3print$$bWiley$$c2015-05-01
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000137908 520__ $$aPreviously, we demonstrated that systemically injected extracellular domain of neuregulin-1β1 (Nrg1β1), a nerve growth and differentiation factor, passes the blood-brain barrier and rescues dopaminergic neurons of substantia nigra in the 6-hydroxydopamine-mouse model of Parkinson's disease (PD). Here, we studied the effects of peripherally administered Nrg1β1 in another toxin-based mouse model of PD. For this purpose, (i) nigrostriatal pathway injury was induced by treatment of adult wild-type mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in acute and subchronic paradigms; and (ii) Nrg1β1 or saline (control) were administered 1 h before each MPTP injection. We found that Nrg1β1 significantly reduced the loss of nigral dopaminergic neurons in both intoxication paradigms (7 days post-injection). However, Nrg1β1 did not reverse MPTP-induced decrease in dopamine levels and dopaminergic fibers in the striatum. We also show that MPTP conversion to its toxic metabolite 1-methyl-4-phenylpyridinium as well as levels of dopamine transporter, mediating intracellular uptake of 1-methyl-4-phenylpyridinium, are unaffected by Nrg1β1. Finally, neuroprotective properties of Nrg1β1 on nigral dopaminergic neurons are specifically mediated by ErbB4 as revealed through the study of ErbB4 knockout mice. In conclusion, systemically administered Nrg1β1 protects midbrain dopaminergic neurons against this PD-related toxic insult. Thus, Nrg1β1 may have a benefit in the treatment of PD patients. Previously, we demonstrated that systemically administered neuregulin-1β1 (Nrg1β1) passes the blood-brain barrier, phosphorylates ErbB4 receptors and elevates dopamine (DA) levels in the nigrostriatal system of healthy mice. Nrg1β1 protects nigral DAergic neurons in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD). Here, we show that Nrg1β1 rescues nigral DAergic neurons also against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cell death. ErbB4 expression is essential for the neuroprotective effect of Nrg1β1 on midbrain DAergic neurons. Nrg1β1 might be beneficial in PD treatment.
000137908 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000137908 542__ $$2Crossref$$i2015-09-01$$uhttp://doi.wiley.com/10.1002/tdm_license_1.1
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000137908 650_7 $$2NLM Chemicals$$aDopamine Agents
000137908 650_7 $$2NLM Chemicals$$aDopamine Plasma Membrane Transport Proteins
000137908 650_7 $$2NLM Chemicals$$aNeuregulin-1
000137908 650_7 $$2NLM Chemicals$$aNeuroprotective Agents
000137908 650_7 $$2NLM Chemicals$$aneuregulin beta
000137908 650_7 $$09P21XSP91P$$2NLM Chemicals$$a1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
000137908 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aErbb4 protein, mouse
000137908 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, ErbB-4
000137908 650_2 $$2MeSH$$a1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: pharmacology
000137908 650_2 $$2MeSH$$aAnimals
000137908 650_2 $$2MeSH$$aAnimals, Genetically Modified
000137908 650_2 $$2MeSH$$aDisease Models, Animal
000137908 650_2 $$2MeSH$$aDopamine Agents: pharmacology
000137908 650_2 $$2MeSH$$aDopamine Plasma Membrane Transport Proteins: metabolism
000137908 650_2 $$2MeSH$$aDopaminergic Neurons: drug effects
000137908 650_2 $$2MeSH$$aMPTP Poisoning: chemically induced
000137908 650_2 $$2MeSH$$aMPTP Poisoning: pathology
000137908 650_2 $$2MeSH$$aMale
000137908 650_2 $$2MeSH$$aMice
000137908 650_2 $$2MeSH$$aMice, Inbred C57BL
000137908 650_2 $$2MeSH$$aNeuregulin-1: pharmacology
000137908 650_2 $$2MeSH$$aNeuregulin-1: therapeutic use
000137908 650_2 $$2MeSH$$aNeuroprotective Agents: pharmacology
000137908 650_2 $$2MeSH$$aNeuroprotective Agents: therapeutic use
000137908 650_2 $$2MeSH$$aReceptor, ErbB-4: deficiency
000137908 650_2 $$2MeSH$$aReceptor, ErbB-4: genetics
000137908 650_2 $$2MeSH$$aSubstantia Nigra: pathology
000137908 650_2 $$2MeSH$$aTime Factors
000137908 7001_ $$0P:(DE-2719)2810437$$aRösler, Thomas W$$b1$$udzne
000137908 7001_ $$0P:(DE-HGF)0$$ade Andrade, Anderson$$b2
000137908 7001_ $$0P:(DE-HGF)0$$aOertel, Wolfgang H$$b3
000137908 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b4$$eLast author$$udzne
000137908 77318 $$2Crossref$$3journal-article$$a10.1111/jnc.13026$$b : Wiley, 2015-01-26$$n4$$p590-597$$tJournal of Neurochemistry$$v133$$x0022-3042$$y2015
000137908 773__ $$0PERI:(DE-600)2020528-4$$a10.1111/jnc.13026$$gVol. 133, no. 4, p. 590 - 597$$n4$$p590-597$$q133:4<590 - 597$$tJournal of neurochemistry$$v133$$x0022-3042$$y2015
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