Lesion of the locus coeruleus aggravates dopaminergic neuron degeneration by modulating microglial function in mouse models of Parkinson׳s disease

Brain Research
Ning YaoQunyuan Xu

Abstract

The degeneration of noradrenergic neurons in the locus coeruleus (LC) commonly occurs in patients with Parkinson's disease (PD), which is characterized by a selective injury of dopaminergic neurons in the substantia nigra (SN). The pathological impact of the LC on the SN in the disease is unknown. In the present study, we used a noradrenergic toxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), to deplete noradrenaline (NA) derived from the LC to explore its influence on degeneration or injury of dopaminergic neurons in the SN in mouse model produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or lipopolysaccharide (LPS). Our results demonstrated that lesion of the LC could change microglial function in the brain, which led to enhanced or prolonged expression of pro-inflammatory cytokines, diminished neurotrophic factors, and weakened ability of anti-oxidation in the SN. The in vitro experiments further confirmed that NA could reduce the inflammatory reaction of microglia. The selective injury of dopaminergic neurons by inflammation, however, was due to the inflammation in different brain regions rather than the depletion of NA. Our results indicate that the lesion in the LC is an ...Continue Reading

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Citations

Jun 27, 2017·Acta Pharmacologica Sinica·Qiu-Shuang ZhangNai-Hong Chen
Dec 8, 2016·Neuropharmacology·José L M MadrigalJuan C Leza
Apr 3, 2019·Journal of Labelled Compounds & Radiopharmaceuticals·Markus ArtelsmairCharles S Elmore
Oct 3, 2019·The International Journal of Neuroscience·Sarika Singh
May 26, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Michael SommerauerPer Borghammer
Sep 28, 2018·Frontiers in Neuroscience·Laura M ButkovichMalú G Tansey
Jul 9, 2017·Cell and Tissue Research·Eduardo E Benarroch
Jan 9, 2019·Frontiers in Cellular Neuroscience·Sara BachillerAntonio Boza-Serrano
Apr 24, 2020·Frontiers in Pharmacology·Elena Paredes-RodriguezCristina Miguelez
Dec 20, 2020·Neurochemistry International·Shuei Sugama, Yoshihiko Kakinuma
Jan 10, 2021·Antioxidants·Pamela J UrrutiaMarco Tulio Núñez
Feb 28, 2021·Scientific Reports·Maria Paola Tramonti FantozziDiego Manzoni
Apr 29, 2020·Neuroscience Letters·G AlbertiniA Roumier

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