Blocking of canonical Notch signaling in dopaminergic neurons prevents its loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

WANG Peng-xiang CHI Yi-li ZHANG Chan NIU Xue-yuan DING Yu-qiang LIAO Min*

doi:10.16098/j.issn.0529-1356.2017.04.006

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Acta Anatomica Sinica ›› 2017, Vol. 48 ›› Issue (4) : 404-409. DOI: 10.16098/j.issn.0529-1356.2017.04.006

Blocking of canonical Notch signaling in dopaminergic neurons prevents its loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

WANG Peng-xiang¹CHI Yi-li¹ ZHANG Chan¹ NIU Xue-yuan¹ DING Yu-qiang² LIAO Min^1*

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Abstract

Objective To investigate the impact of blocking of Notch signaling pathway (loss of expression of Notch signaling pathway) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage to midbrain dopaminergic neurons. Methods Both 5-month-old TH-Cre Rbpj gene knockout mice and wild type mice (n=48) were injected intraperitoneally with MPTP to produce a Parkinson’s disease (PD) animal model, then a variety of methods including behavioral test, immunohistochemistry and Western blotting were used to investigate the role of Notch signaling pathway in MPTP-induced loss of dopaminergic neurons in mouse midbrain. Results When treated with MPTP, Rbpj CKO mice exhibited better locomotor functions than wild type mice. Rbpj CKO mice were found to have fewer substantia nigra pars compacta (SNpc)neurons than wild type mice. After MPTP injection, the number of dopaminergic neurons were drastically reduced in wild type mice while in Rbpj CKO mice the number of these neurons remained virtually unchanged. Western blotting result showed that there was a significant increase in NICD-1 expression in both Rbpj CKO mice and wild-type mice, the increase was more profound in Rbpj CKO mice. Conclusion The deletion of Notch signaling pathway can lead to reduction in dopaminergic neurons, and deletion of Notch signaling pathway can reduce MPTP induced damage to dopaminergic neurons.

Key words

Notch signaling pathway

/ 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Parkinson’s disease / Dopaminergic neuron / Immunohistochemistry / Mouse

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WANG Peng-xiang CHI Yi-li ZHANG Chan NIU Xue-yuan DING Yu-qiang LIAO Min.

Blocking of canonical Notch signaling in dopaminergic neurons prevents its loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

[J]. Acta Anatomica Sinica. 2017, 48(4): 404-409 https://doi.org/10.16098/j.issn.0529-1356.2017.04.006

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