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Séminaire impromptu - Claude MESSIEROligodendrocyte progenitor cells as source of neurons in the adult brain

Abstract :

 Oligodendrocyte progenitor cells (OPCs; also known as NG2-glial cells, synantocytes, or polydendrocytes) are a type of glial cells that give rise, as their name suggests, to myelinating oligodendrocytes during early stages of post-natal life. Interestingly, a large number of OPCs remain undifferentiated after developmental myelination is completed, and OPCs correspond to 2-9% of the total cell population of the adult brain. While their proliferative activity does decline with age due to a slowing down of the cell cycle, they continue to undergo cell division in the adult brain, representing the mature brain’s most active population of cycling cells. The primary fates of daughter cells of adult OPCs are self-renewal and oligodendrocyte differentiation, although there is a debate as to their ability to also differentiate into astrocytes and neurons. We used the NG2-CreERTM:EYFP reporter mouse to estimate the total number of OPCs in the corpus callosum and cortex of the adult mouse and determine the proportion of proliferating adult OPCs and their fate. We found that 1) white and grey matter OPCs have different properties, 2) OPCs continue to differentiate into oligodendrocytes into adulthood, and 3) provide evidence for the neuronal differentiation of adult OPCs in cortical grey matter. However, we found no evidence that reference memory training modulates the proliferation and differentiation of adult OPCs. We also found some evidence that GABAA-receptor agonism plays a modulatory role on adult OPC proliferation and differentiation. Neuron-OPC pairs have been noted in previous reports so we used stereological procedures to estimate of the total number of OPC-neuron pairs in the cortex of the adult mouse. We found that the neurons in these pairs are most likely GABAergic interneurons. We estimate that 40% of GABAergic neurons in the mouse cortex have closely-apposed OPC satellite cells. There is some evidence that modulation of GABAergic neurotransmission changes the total number of OPC-neuron pairs. 

Selected publications

Boulanger, J.J.* and C. Messier. Doublecortin in oligodendrocyte precursor cells in the adult mouse brain. Frontiers in Neuroscience (Neurogenesis). 11, 2017, 143. doi: 10.3389/fnins.2017.00143

Béland-Millar, A.*, J. Larcher*, J. Courtemanche*, T. Yuan*, and C. Messier. Effects of systemic metabolic fuels on glucose and lactate levels in the brain extracellular compartment in the mouse. Frontiers in Neuroscience (Neuroenergetics, Nutrition and Brain Health), 11, 2017.

Granger, M.W.** , B. Franko, M.W. Taylor, C. Messier, P. St George-Hyslop, S.A.L. Bennett. The TgCRND8 mouse model of Alzheimer’s disease exhibits sexual dimorphisms in behavioral indices of cognitive reserve. Journal of Alzheimer’s Disease. vol. 51(3), 2016, 757-773.

Boulanger, J.J.* and C. Messier. From precursors to myelinating oligodendrocytes: Contribution of intrinsic and extrinsic factors to white matter plasticity in the adult brain. Neuroscience, 269, 2014, 343-366. doi:10.1016/j.neuroscience.2014.03.063.