Metabotropic glutamate receptors in oligodendrocytes and astrocytes in white and grey matter brain regions
Student thesis: Doctoral Thesis
Glial cells express a wide range of neurotransmitter receptors throughout the central nervous system (CNS). In this thesis, I have investigated glial neurotransmitter signaling mechanisms in CNS white matter, using the mouse optic nerve as a model white matter and with a particular focus on metabotropic glutamate receptors (mGluR). The transcriptomic profiling of postnatal, adult and ageing optic nerve identified a pre-eminence of glutamatergic neurotransmission in the optic nerve and highlighted a switch to GABAergic signaling in the ageing white matter, without a loss of glutamatergic neurotransmission. Immunostaining showed expression of group I and group II mGluR in optic nerve astrocytes and oligodendrocytes and their functionality was demonstrated by live cell calcium imaging. Activation of group I and group II mGluR is shown to protect both oligodendrocytes and astrocytes from hypoxia/ischaemia, using an oxygen and glucose deprivation (OGD) model in the isolated intact mouse optic nerve. A key finding is that mGluR were expressed by glia at all ages and were not developmentally downregulated, as had been suggested from previous in vitro studies. In addition, the genomic analysis indicated disruption of OPCs in ageing tissue, and significant age-related disruption of OPCs was confirmed in the triple transgenic mouse model of Alzheimer’s disease (3xTg AD). This study provides new insight into mGluR expression and function in white matter glia.
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