Tags

Type your tag names separated by a space and hit enter

Defective autophagy is associated with neuronal injury in a mouse model of multiple sclerosis.
Bosn J Basic Med Sci 2017; 17(2):95-103BJ

Abstract

Neurodegeneration, along with inflammatory demyelination, is an important component of multiple sclerosis (MS) pathogenesis. Autophagy is known to play a pivotal role in neuronal homeostasis and is implicated in several neurodegenerative disorders. However, whether autophagy is involved in the mechanisms of neuronal damage during MS remains to be investigated. Experimental autoimmune encephalomyelitis (EAE), an in vivo model of MS, was induced in female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein p35-55. After that, autophagic flux in the spinal cord of mice was evaluated by detection of LC3-II and Beclin1 protein expressions. EAE mice were then administered with rapamycin and 3-methyladenine (3-MA) for 10 days. Afterward, the changes in LC3-II, Beclin1, and p62 expression, number of infiltrated inflammatory cells, demyelinated lesion area, and neuronal damage, as well as clinical scores, were assessed. Further, apoptotic cell rate and apoptosis-related protein expressions were monitored. We observed an impaired autophagic flux and increased neuronal damage in the spinal cords of EAE mice. We also found that rapamycin, an autophagy inducer, mitigated EAE-induced autophagy decrease, inflammation, demyelination and neuronal injury, as well as the abnormal clinical score. In addition, rapamycin suppressed cell apoptosis, and decreased Bax/Bcl-2 ratio and cleaved caspase-3 expression. Conversely, the effect of autophagy inhibitor 3-MA on EAE mice resulted in completely opposite results. These results indicated that autophagy deficiency, at least in part, contributed to EAE-induced neuronal injury and that pharmacological modulation of autophagy might be a therapeutic strategy for MS.

Authors+Show Affiliations

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. fengxuedan111@sina.com.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28086065

Citation

Feng, Xuedan, et al. "Defective Autophagy Is Associated With Neuronal Injury in a Mouse Model of Multiple Sclerosis." Bosnian Journal of Basic Medical Sciences, vol. 17, no. 2, 2017, pp. 95-103.
Feng X, Hou H, Zou Y, et al. Defective autophagy is associated with neuronal injury in a mouse model of multiple sclerosis. Bosn J Basic Med Sci. 2017;17(2):95-103.
Feng, X., Hou, H., Zou, Y., & Guo, L. (2017). Defective autophagy is associated with neuronal injury in a mouse model of multiple sclerosis. Bosnian Journal of Basic Medical Sciences, 17(2), pp. 95-103. doi:10.17305/bjbms.2017.1696.
Feng X, et al. Defective Autophagy Is Associated With Neuronal Injury in a Mouse Model of Multiple Sclerosis. Bosn J Basic Med Sci. 2017 May 20;17(2):95-103. PubMed PMID: 28086065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defective autophagy is associated with neuronal injury in a mouse model of multiple sclerosis. AU - Feng,Xuedan, AU - Hou,Huiqing, AU - Zou,Yueli, AU - Guo,Li, Y1 - 2017/05/20/ PY - 2016/09/29/received PY - 2016/11/15/accepted PY - 2017/01/09/revised PY - 2017/1/14/pubmed PY - 2018/3/24/medline PY - 2017/1/14/entrez SP - 95 EP - 103 JF - Bosnian journal of basic medical sciences JO - Bosn J Basic Med Sci VL - 17 IS - 2 N2 - Neurodegeneration, along with inflammatory demyelination, is an important component of multiple sclerosis (MS) pathogenesis. Autophagy is known to play a pivotal role in neuronal homeostasis and is implicated in several neurodegenerative disorders. However, whether autophagy is involved in the mechanisms of neuronal damage during MS remains to be investigated. Experimental autoimmune encephalomyelitis (EAE), an in vivo model of MS, was induced in female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein p35-55. After that, autophagic flux in the spinal cord of mice was evaluated by detection of LC3-II and Beclin1 protein expressions. EAE mice were then administered with rapamycin and 3-methyladenine (3-MA) for 10 days. Afterward, the changes in LC3-II, Beclin1, and p62 expression, number of infiltrated inflammatory cells, demyelinated lesion area, and neuronal damage, as well as clinical scores, were assessed. Further, apoptotic cell rate and apoptosis-related protein expressions were monitored. We observed an impaired autophagic flux and increased neuronal damage in the spinal cords of EAE mice. We also found that rapamycin, an autophagy inducer, mitigated EAE-induced autophagy decrease, inflammation, demyelination and neuronal injury, as well as the abnormal clinical score. In addition, rapamycin suppressed cell apoptosis, and decreased Bax/Bcl-2 ratio and cleaved caspase-3 expression. Conversely, the effect of autophagy inhibitor 3-MA on EAE mice resulted in completely opposite results. These results indicated that autophagy deficiency, at least in part, contributed to EAE-induced neuronal injury and that pharmacological modulation of autophagy might be a therapeutic strategy for MS. SN - 1840-4812 UR - https://www.unboundmedicine.com/medline/citation/28086065/Defective_autophagy_is_associated_with_neuronal_injury_in_a_mouse_model_of_multiple_sclerosis_ L2 - https://doi.org/10.17305/bjbms.2017.1696 DB - PRIME DP - Unbound Medicine ER -