UB Study Seeks Molecular Mechanism Leading to Myelination

The research may lead to a better understanding of how myelin—a nerve-protecting substance lost or damaged in degenerative diseases, including multiple sclerosis—can be restored or repaired.

The five-year grant is from the National Institute of Neurological Disorders and Stroke.

Through the project, Paez will study how voltage-operated calcium channels (VOCCs) regulate the maturation of oligodendrocytes, the myelinating cells of the central nervous system.

“This research will contribute significantly to our understanding of the fundamental role of VOCCs in the complex physiological environment of development, disease and repair,” says Paez.

The study builds on Paez’s prior research that found these channels play a role in the calcium homeostasis of myelinating cells.

“Perturbation of calcium 2 plus (Ca++) homeostasis likely plays an important role in the pathogenesis underlying neurodegenerative and demyelinating diseases,” he says.

Paez’s project involves both in vivo and in vitro experiments.

Lab experiments will involve reducing the expression of VOCCs in oligodendrocytes to see if these channels play a key role in triggering the maturation of myelinating cells.

Using a co-culture system of oligodendrocyte progenitor cells (OPCs) and cortical neurons, the researchers also will test whether the Ca++ channels facilitate axo-glial signaling during the first steps of myelin formation.

In addition, a demyelination model will be used to examine how the ablation of these calcium channels affects myelin loss and recovery.

Through animal studies, the research team will silence the expression of Ca++ channels in progenitor cells to test if the entry of voltage-gated Ca++ promotes the cells’ survival and maturation in the remyelinating adult brain.

“Our preliminary findings indicate a role for VOCCs as a potential modulator of OPC development in the adult mouse brain in acute demyelination,” says Paez.

The Paez lab is located in the Hunter James Kelly Research Institute, a partnership between the School of Medicine and Biomedical Sciences and the Hunter’s Hope Foundation.

The institute supports basic and clinical research related to the cause, prevention and treatment of myelin-related diseases, such as Krabbe and other leukodystrophies, multiple sclerosis and hereditary neuropathies.

Paez is collaborating with Lawrence Wrabetz, MD, professor of neurology and biochemistry, who directs the institute, and Veronica Cheli, PhD, a senior researcher in pharmacology and toxicology.