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UBC Theses and Dissertations

Role of galectin-1 in sensory neuron development and peripheral nerve repair Gaudet, Andrew David


In comparison to adult central nervous system (CNS) axons, peripheral nervous system (PNS) axons have a high propensity for regrowth following injury. The PNS axon’s capacity to regenerate depends on an effective response within the neuron itself, combined with a supportive environment maintained by cells surrounding the axon. Unfortunately, successful reconnection of peripheral axons with appropriate targets is hampered by discontinuities associated with injury and by a decreased growth response over time. Studying strategies that improve peripheral nerve repair could enhance functional outcomes following peripheral nerve injury (PNI), and might provide insight for CNS repair. The small protein galectin-1 (Gal1) is required for developmental targeting of specific olfactory axons and promotes peripheral axon regeneration. Despite this, Gal1’s role in sensory axon development and regeneration is not well-defined. In this dissertation, I explore how Gal1 affects developmental and regenerative axon growth. Using mice lacking Gal1 (Lgals1-/-), I show that Gal1 is required for proper targeting of central axons of small-diameter, nociceptive dorsal root ganglion (DRG) neurons. Interestingly, Lgals1-/- mice had corresponding deficits in behavioural responses to noxious stimuli. Next, I characterize the regulation of Gal1 in DRG neurons and their environment following PNI and dorsal root injury (DRI). DRG neurons mount a robust regenerative response following injury of their peripheral, but not central branch. Neuronal Gal1 was upregulated after PNI, but not DRI. In addition, Gal1 expression in the regrowing axon’s environment correlated with the permissiveness of that environment. I then examine whether Gal1 promotes axonal regeneration through mechanisms intrinsic and/or extrinsic to the injured neuron. Gal1 did not affect DRG neurons’ intrinsic growth state: Lgals1-/- neurons did not display abnormal neurite outgrowth, and exogenous oxidized Gal1 (Gal1/Ox) did not affect neurite outgrowth. Gal1 does affect the response of non-neuronal cells. I show that Gal1 promotes accumulation of immune cells called macrophages following PNI. Injection of Gal1-specific antibodies attenuated typical PNI-induced accumulation of macrophages; conversely, Gal1/Ox injection into uninjured nerves facilitated macrophage accumulation in wild-type mice. My data suggest that Gal1 does not elicit axon growth directly; rather, Gal1 likely promotes axon regeneration indirectly by enhancing PNI-induced macrophage accumulation.

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