Grant: Operating Grant - PA: Regional Partnership Program - Saskatchewan

Oligodendrocytes (OLs) are a cell type in the central nervous system (CNS) that can readily be induced to wrap axons (a long filament that extends from nerve cells) in a smooth fatty protein called myelin. Myelin insulates the axon and is critical for all bodily movements and functions. The myelinating ability of OLs is essential to the proper repair of CNS injury and yet the efficiency of OL remyelination declines with age. This age related impairment of remyelination is relevant to multiple sclerosis (MS), from which patients may suffer for several decades, and to cognitive impairments accompanying several neurological disorders, including Alzheimer's disease (AD), Parkinson's disease, and schizophrenia. Little is known about the specific role(s) played by the factors that govern the expression of genes needed for OLs to myelinate axons. The objective of our research is to determine how myelination is affected by altering the expression of two genes (Hoxd1 and Nkx2.2) and the enzyme Sirtuin 2 (Sirt2). Sirtuins have been shown to increase longevity of yeast, worms, and fruit-flies. We hypothesize these genes and enzyme play important roles in controlling the progression of OLs from immature cells to ones that have assembled a myelin sheath, and that OL myelination/remyelination will be affected during aging in mice as a consequence of impaired Hoxd1 and Nkx2.2 control. Our long-term goal is to determine how Hoxd1, Nkx2.2, and Sirt2 regulate myelination by OLs. Establishing how these factors regulate this process is important for determining how to increase remyelination of damaged CNS axons and reverse the age-related decline in remyelination efficiency. This research is the groundwork for developing therapeutic approaches to repair CNS damage caused by MS or several age-related diseases including AD.