Journal
BRAIN RESEARCH
Volume 1625, Issue -, Pages 255-274Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2015.08.032
Keywords
Parkinson's disease; Locus coeruleus; Microglia; Substantia nigra; Striatum; Inflammation
Categories
Funding
- Major State Basic Research Development Program of China (973 Program) [2006CB500700, 2011CB504100]
- National Natural Science Foundation of China [30430280]
- Beijing Committee of Science and Technology [Z0005187040311]
- Research Fund of Capital Medical University [2014ZR03]
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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 important factor in promoting dopaminergic neuron degeneration by impacting the function of microglia in the midbrain. (C) 2015 Elsevier B.V. All rights reserved.
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