BMAL1 regulation of microglia-mediated neuroinflammation in MPTP-induced Parkinson's disease mouse model.

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.

Light therapy: a new option for neurodegenerative diseases.

ABSTRACT: Given the increasing incidence of neurodegenerative disease (ND), recent research efforts have intensified the search for curative treatments. Despite significant research, however, existing therapeutic options for ND can only slow down the progression of the disease, but not provide a cure. Light therapy (LT) has been used to treat some mental and sleep disorders. This review illustrates recent studies of the use of LT in patients with ND and highlights its potential for clinical applications. The literature was collected from PubMed through June 2020. Selected studies were primarily English articles or articles that could be obtained with English abstracts and Chinese main text. Articles were not limited by type. Additional potential publications were also identified from the bibliographies of identified articles and the authors' reference libraries. The identified literature suggests that LT is a safe and convenient physical method of treatment. It may alleviate sleep disorders, depression, cognitive function, and other clinical symptoms. However, some studies have reported limited or no effects. Therefore, LT represents an attractive therapeutic approach for further investigation in ND. LT is an effective physical form of therapy and a new direction for research into treatments for ND. However, it requires further animal experiments to elucidate mechanisms of action and large, double-blind, randomized, and controlled trials to explore true efficacy in patients with ND.