The Role and Distribution of Ionotropic Glutamate Receptors on Peripheral Myelinated Axons
Date
2015-01-08
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Abstract
The nervous system consists of both central and peripheral components. The CNS white matter and the PNS nerves consist of myelinated and unmyelinated axons, which play the critical role of transmitting electrical impulses. Axons from the CNS and PNS share many physiological similarities. The axons can be compromised in a number of neurological conditions such as stroke, spinal cord injury, multiple sclerosis and various peripheral neuropathies. Limited knowledge about the pathophysiological mechanisms of injury to non-neuronal cells, and in particular axons, exists. This thesis investigates the presence and function of ionotropic glutamatergic and purinergic receptors on PNS myelinated axons in relation to axonal Ca2+ dynamics and structural changes. To generalize these observations, the presence of glutamate receptor expression in human CNS white matter is also explored.
Immunohistochemistry was used to detect the presence of glutamate receptors in rodent spinal roots and in human white matter. Transgenic mice, expressing an endogenous FRET-based Ca2+ biosensor, were used to visualize axonal Ca2+ dynamics in response to glutamatergic and purinergic receptor stimulation. Myelinic and axonal damage in response to glutamate receptors was quantitated using a 2D-FFT-based image analysis method.
NMDA and AMPA receptors are present on PNS myelinated axons and in human CNS white matter. Glutamate and the more specific agonists NMDA and AMPA induce axonal Ca2+ changes. NMDA receptor activation induces morphological changes in axons and myelin, while AMPA receptor activation does not. Ionotropic purinergic receptor signalling is likely present in myelinated axons, but the mechanisms remain unclear.
The data presented in this thesis support the notion of an axo-myelinic synapse using classical neurotransmitters by identifying receptors and effects of receptor activation in myelinated axons. The results highlight the importance of NMDA receptors in axo-glial signalling in the PNS. Glutamatergic signalling in the PNS may have important implications for PNS development, pathophysiology of peripheral neuropathies and for the understanding of PNS regeneration. Furthermore, the work presented here could be significant for the CNS, given the similarities in the physiology of CNS and PNS myelinated fibres.
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Neuroscience
Citation
Christensen, P. C. (2015). The Role and Distribution of Ionotropic Glutamate Receptors on Peripheral Myelinated Axons (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28314