Thesis topic proposal
Mónika Sztretye
Assessing the ability of cannabinoids to correct the calcium fluxes in skeletal muscle fibers from mdx mice


Institute: University of Debrecen
theoretical medicine
Doctoral School of Molecular Medicine

Thesis supervisor: Mónika Sztretye
Location of studies (in Hungarian): University of Debrecen, Faculty of Medicine, Department of Physiology
Abbreviation of location of studies: DEÉI

Description of the research topic:

Some of myopathies are hereditary (muscle dystrophies), but they can also be caused by metabolic diseases, inflammation, and cancer. The most common inherited myopathy is Duchenne Muscular Dystrophy (DMD), which affects 1: 3500 new-born babies. DMD is a genetic disorder characterized by progressive muscle degeneration and weakness due to the lack of a protein called dystrophin. In skeletal muscle, mitochondria occupy about 10–15% of the volume of muscle fibers (Eisenberg, 1983) and are major sources of ATP as well as reactive oxygen species (ROS) production. Previous studies have suggested mitochondrial disorders for the development of oxidative stress-related diseases (Sies et al. 2017), indicating that they may also play a role in the pathomechanism of DMD. The endocannabinoid system (ECS) refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. Iannotti et al. (2018) recently reported the role of cannabinoid receptor 1 (CB1R) in the development of degenerative muscle diseases. In our experiments, we intend to use a dual transgenic mouse model carrying the mdx and mt-cpYFP mutations. In transgenic mice produced in the laboratory of Dr. Jingsong Zhou (University of Arlington, Texas, USA), mt-cpYFP detects dynamic changes in ROS-associated mitoflash events at the level of individual mitochondria. Thus, the study of mitoflash activities provides an unique opportunity to investigate whether the use of CB1R antagonists can reverse or slow down mitochondrial dysfunction observed in mdx mice.

Specific aim #1. To determine the role of ECS in skeletal excitation-contraction coupling processes in reversing/slowing down the muscle dysfunction of mdx mice following synthetic and/or plant derived CB1R antagonist(s) treatment with emphasis on their ability to correct the aberrant calcium fluxes across cellular membranes.

Specific aim #2. Measurement of mitochondrial [Ca2+] and mitoflash activity in fibers isolated from CB1 antagonist-treated or untreated double transgenic mdx/cpYFP mice.

Required language skills: English intermediate level
Number of students who can be accepted: 1

Deadline for application: 2021-08-15

2021. X. 14.
ODT online ülés
Az ODT következő, online ülésére 2021. november 19-én 10.00 órakor kerül sor.

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