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Physical activity heterogenously modulates NG2-glia population behavior, and is necessary for cognitive enhancement
Physical activity heterogenously modulates NG2-glia population behavior, and is necessary for cognitive enhancement
NG2-glia is a macroglial population, which constitutes about 5-10% of the total cell population in the mammalian brain. These cells have “stem cell-like” features; for instance, they can proliferate and self-renew and they mostly differentiate into oligodendrocytes, a cell type are of great importance as they myelinate axons in the central nervous system, a process essential for the proper function of vertebrates’ nervous system. Although most myelination happens after birth and completed at a young age, it has been shown that it can also occur during adulthood in mammals. Adult myelination can be modulated by experience, but the exact mechanism of this phenomenon remains unclear. Hence, it is thought that neuronal activity could stop the proliferation and promote the differentiation of NG2-glia, and in turn, newly generated oligodendrocytes could provide the new myelin. However, it is still unclear how neuronal activity could lead to changes in NG2-glia behavior in the adult mouse. In this doctoral thesis, I have used a voluntary physical activity (VPA) mouse model to study the effects of experience on NG2-glia, although other mechanism cannot be discarded. Indeed, our results showed an increase in the proliferation and differentiation of NG2-glia in the cerebral cortical grey matter but not in the corresponding white matter after VPA. We also observed that NG2-glia tend to differentiate with two different modalities, and one of them is preferred during VPA. Furthermore, I performed mass spectrometry of sorted NG2-glia to profile them after VPA, and found that the remaining, non-differentiated NG2-glia show less myelin-related proteins. Interestingly, the results of the proteome analysis correlate with the increase in the number of the GPR17+ subset of NG2-glia, which is characterized by its slow differentiation rate, and I observed that this population remains mostly unaffected by VPA. Finally, for the first time, I found that newly generated oligodendrocytes integrate into the circuitry of the cortex and this myelin remodeling contributes in cognitive enhancement induced by exercise.
NG2-glia, Oligodendrocytes, Myelin, Physical activity, cognitive enhancement
Eugenin von Bernhardi, Jaime
2020
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Eugenin von Bernhardi, Jaime (2020): Physical activity heterogenously modulates NG2-glia population behavior, and is necessary for cognitive enhancement. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)
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Abstract

NG2-glia is a macroglial population, which constitutes about 5-10% of the total cell population in the mammalian brain. These cells have “stem cell-like” features; for instance, they can proliferate and self-renew and they mostly differentiate into oligodendrocytes, a cell type are of great importance as they myelinate axons in the central nervous system, a process essential for the proper function of vertebrates’ nervous system. Although most myelination happens after birth and completed at a young age, it has been shown that it can also occur during adulthood in mammals. Adult myelination can be modulated by experience, but the exact mechanism of this phenomenon remains unclear. Hence, it is thought that neuronal activity could stop the proliferation and promote the differentiation of NG2-glia, and in turn, newly generated oligodendrocytes could provide the new myelin. However, it is still unclear how neuronal activity could lead to changes in NG2-glia behavior in the adult mouse. In this doctoral thesis, I have used a voluntary physical activity (VPA) mouse model to study the effects of experience on NG2-glia, although other mechanism cannot be discarded. Indeed, our results showed an increase in the proliferation and differentiation of NG2-glia in the cerebral cortical grey matter but not in the corresponding white matter after VPA. We also observed that NG2-glia tend to differentiate with two different modalities, and one of them is preferred during VPA. Furthermore, I performed mass spectrometry of sorted NG2-glia to profile them after VPA, and found that the remaining, non-differentiated NG2-glia show less myelin-related proteins. Interestingly, the results of the proteome analysis correlate with the increase in the number of the GPR17+ subset of NG2-glia, which is characterized by its slow differentiation rate, and I observed that this population remains mostly unaffected by VPA. Finally, for the first time, I found that newly generated oligodendrocytes integrate into the circuitry of the cortex and this myelin remodeling contributes in cognitive enhancement induced by exercise.