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CNS Neurosci Ther. 2019 Jul 18. doi: 10.1111/cns.13182. [Epub ahead of print]

Therapeutic effects of hirsutella sinensis on the disease onset and progression of amyotrophic lateral sclerosis in SOD1G93A transgenic mouse model.

Shang HY1,2,3, Zhang JJ1,2,4, Fu ZF1,2, Liu YF1,2, Li S1,2, Chen S5, Le WD1,2.

Author information

1
Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
2
Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
3
General Hospital of Yangtze River Shipping, Wuhan Brain Hospital, Wuhan, China.
4
Chifeng Municipal Hospital, Chifeng, China.
5
Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

AIMS:

Although the pathophysiology of amyotrophic lateral sclerosis (ALS) is still not completely understood, the deregulated microglia polarization and neuroinflammation have been shown to contribute to the pathogenesis and progression of this disease. In the present study, we aimed to determine whether hirsutella sinensis (HS) could reduce neuroinflammatory and pathological changes in the spinal cord of SOD1G93A model mice of ALS and consequently ameliorate disease onset and progression.

METHODS:

SOD1G93A mice were chronically treated with HS by gavage. Their lifespan was recorded, and motor behavior was evaluated by rotarod test. The pathological changes in skeletal muscles and motor neurons in spinal cords were assessed by immunofluorescent staining and hematoxylin-eosin staining. The microglia activation and neuroinflammation were determined by immunofluorescent staining and RT-PCR.

RESULTS:

Our data suggested that repeated HS administration prolonged the lifespan and extended disease duration of ALS mice without significant delay on disease onset. HS ameliorated the pathological changes in the motor neurons and gastrocnemius muscles. Moreover, HS promoted the transition of microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotype in the spinal cord of ALS mice.

CONCLUSION:

All these findings indicate that HS may serve as a potential therapeutic candidate for the treatment of ALS.

KEYWORDS:

SOD1G93A; amyotrophic lateral sclerosis; hirsutella sinensis; microglia; motor neuron; neuroinflammation

PMID:
31318169
DOI:
10.1111/cns.13182

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