Publications by authors named "Shi-Zhuang Wei"

4 Publications

  • Page 1 of 1

Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming.

Aging Cell 2021 May 8:e13375. Epub 2021 May 8.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia-mediated neuroinflammation makes a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)-induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti-inflammatory effects of MT1 activation. LPS-induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS-treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti-inflammatory effects of MT1 activation were observed in LPS-stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS-induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti-inflammation.
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http://dx.doi.org/10.1111/acel.13375DOI Listing
May 2021

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

FASEB J 2020 05 4;34(5):6570-6581. Epub 2020 Apr 4.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

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.
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http://dx.doi.org/10.1096/fj.201901565RRDOI Listing
May 2020

Impact of Maternal Separation on Dopamine System and its Association with Parkinson's Disease.

Neuromolecular Med 2020 09 13;22(3):335-340. Epub 2020 Jan 13.

Institute of Neuroscience, Soochow University, Suzhou, 215000, Jiangsu, China.

As a type of stress, maternal separation (MS) has been one of the most widely used models in neuropsychiatric research. An increasing number of studies has found that MS not only affects the function of the hypothalamic-pituitary-adrenal axis and hippocampal 5-hydroxytryptamine system, but also causes dysfunction of the central dopamine (DA) system and increases the susceptibility of dopaminergic neurons to pathogenic factors of Parkinson's disease (PD), for instance, 6-hydroxydopamine, thus impairing motor function. We reviewed the impact of MS on the DA system and its correlation with PD and found the following: (1) discrepant effects of MS on the DA system have been reported; (2) MS is a good model to study the impact of stress on the occurrence and development of PD, however, unified modeling criteria of MS are required; (3) correlation between MS and PD may involve the impact of MS on the DA system, which however is not the only connection; (4) intervening measures can block pathways between MS and PD, which provides reference for the prevention of PD in specific populations such as left-behind children.
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http://dx.doi.org/10.1007/s12017-019-08587-xDOI Listing
September 2020

Sleep deprivation caused a memory defects and emotional changes in a rotenone-based zebrafish model of Parkinson's disease.

Behav Brain Res 2019 10 10;372:112031. Epub 2019 Jun 10.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China. Electronic address:

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world. Apart from motor deficits, PD reduces patient's quality of life through sleep disturbances, cognitive impairment and emotional disorders. However, it's unclear whether bad life habits such as stay up late exacerbate the patient's cognition and emotional disorders. Thus we investigated the consequences of sleep deprivation (SD) on memory and emotions using a rotenone-based zebrafish model of PD. Behavioral assays, using locomotor activity assay, showed that rotenone treated zebrafish exhibited PD-like symptoms, whereas sleep deprivation didn't exacerbate the progression of them. The object discrimination task exhibited that the short-term cognitive deficits of rotenone group are more serious than the sham group after SD. Light-dark box test showed that rotenone treated fish are more dysphoric than the sham fish after SD. Dopamine and DOPAC significantly reduced in rotenone treated fish compared with the sham fish. However, this DOPAC reduction recovered after SD. The expression of D2 and D3 in rotenone treated zebrafish elevated compared with sham group and SD group. However, the rotenone treated zebrafish manifested a decrease level of D2 and D3 after SD. D1 did not show any significantly changes among the four groups. Our findings suggest that zebrafish treated with rotenone may have a more severe damage of memory and emotional function after SD, which may be related to the changes in the DA systems.
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http://dx.doi.org/10.1016/j.bbr.2019.112031DOI Listing
October 2019