UBC Theses and Dissertations
Galectin-1 in injury and regeneration McGraw, John
In higher vertebrates, injury to both sensory and motor axons within the central nervous system (CNS) results in permanent loss of sensation and paralysis. In contrast, peripheral nervous system (PNS) injuries are often followed by functional recovery. This disparity in the regenerative ability of the PNS and CNS is attributed to both the intrinsic gene response of injured neurons and the environment across which an injured axon must extend in order for successful regeneration to occur. Recent reports demonstrate that the carbohydrate-binding protein galectin (Gal)-l, which is expressed during the development of sensory and motor neurons and in the mature adult, is involved in regrowth of axotomized neurons following a peripheral nerve injury. Specifically, exogenous application of recombinant Gall to injured peripheral nerves increased the rate of axonal growth into acellular grafts. However, the axotomy-induced changes of endogenous neuronal Gall expression have not been examined. In this thesis, I demonstrate that axotomized neurons that were able to regenerate or initiate a growth response also had increased Gall expression. Gall returned to uninjured levels upon target re-innervation suggesting that the target may partially regulate Gall expression. Furthermore, homozygous Gall null mutant (-/-) mice showed an attenuated rate of functional recovery after a nerve crush. I also examined sensory responses of Gall -/- mice, since Gall is expressed during sensory neuronal development as well as within the adult dorsal root ganglion (DRG). The absence of Gall in the Gall -/- mouse led to an increased threshold for thermal nociceptive stimuli. This correlated with differences in nociceptive neuron proportions and their pattern of termination within the spinal cord. Taken together these data underscore an important contribution of endogenous Gall to the regenerative process and to sensory neuronal development and/or maintenance.
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