Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

Calpain-Calpastatin System in Peripheral Nerve Myelination and Demyelination

Drouet Saltos, Domenica Elizabeth
http://orcid.org/0000-0002-3032-4140
http://rave.ohiolink.edu/etdc/view?acc_num=wright1559220437439116

Abstract Details

2019, Master of Science (MS), Wright State University, Anatomy.
Myelin is the structure formed by glial cells that electrically insulates axons aiding in propagation of action potentials. Disruption of myelin sheath (demyelination) is common to neurological diseases, such as multiple sclerosis (MS). The calcium-dependent protease, calpain, is known to modulate myelination during central nervous system (CNS) development. Endogenous calpain inhibitor, calpastatin, regulates calpain activity. The calpain-calpastatin system has been implicated in the CNS demyelination occurring in diseases. Charcot-Marie-Tooth disease (CMT) is a hereditary demyelinating polyneuropathy affecting proper functioning of peripheral nerves, demonstrating the importance of myelin in the peripheral nervous system (PNS). However, calpain’s role in the mechanism(s) of PNS myelination and demyelination remain unclear. To characterize calpain-calpastatin system in the PNS, the present study utilized immunoblotting to quantify protein levels of major calpains in the nervous system, calpain-1 and calpain-2, in both healthy and injured rodent. Our results show that the expression of both calpain-1 and calpain-2 increased throughout early development when myelin is actively formed in rat sciatic nerves. In contrast to the previous observations in the literature showing an increase of calpains in MS brain tissues; we observed a decrease in protein levels in both calpain-1 and calpain-2 during the PNS acute demyelination phase induced by lysolecithin injection. We analyzed sciatic nerves from Trembler-J mice, a model of a human hereditary demyelinating neuropathy. Our data showed an increase of proenzyme and autolytic forms of calpain-1 (p=0.01) and a tendency of reduction of calpain-2 protein expression levels (p=0.06) in Trembler-J mouse sciatic nerves. Importantly, expression of calpastatin was significantly increased in Trembler-J mouse sciatic nerves compared to wild-type (p=0.03), presumably inhibiting calpain over-activation. The observed dynamic changes of calpains and calpastatin strongly suggest that they play a key role in both myelination and demyelination in PNS. Further understanding of PNS myelination and demyelination is critical to future studies aimed at establishing new therapies for currently intractable PNS demyelinating diseases.
Keiichiro Susuki, M.D., Ph.D. (Advisor)
Thomas Brown, Ph.D. (Committee Member)
Kathrin Engisch , Ph.D. (Committee Member)
69 p.
Anatomy and Physiology; Neurosciences
calpain; calpastatin; sciatic nerve; PNS; myelination; demyelination

Recommended Citations

Citations

  • Drouet Saltos, D. E. (2019). Calpain-Calpastatin System in Peripheral Nerve Myelination and Demyelination [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1559220437439116

    APA Style (7th edition)

  • Drouet Saltos, Domenica. Calpain-Calpastatin System in Peripheral Nerve Myelination and Demyelination . 2019. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1559220437439116.

    MLA Style (8th edition)

  • Drouet Saltos, Domenica. "Calpain-Calpastatin System in Peripheral Nerve Myelination and Demyelination ." Master's thesis, Wright State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1559220437439116

    Chicago Manual of Style (17th edition)

wright1559220437439116
109
© 2019, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.