Title:
The Effects of Nerve Injury and Synaptic Preservation on Motoneuron Activity
The Effects of Nerve Injury and Synaptic Preservation on Motoneuron Activity
Author(s)
Garcia, Violet
Advisor(s)
Cope, Timothy C.
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Abstract
Peripheral nerve injury currently has a poor prognosis that often results in motor deficits such as discoordination and co-contraction of muscle antagonists (Brushart, 2011; Horstman et al., 2019). Because of this, studying the effects of peripheral nerve injury on the morphology and functional connectivity of the central nervous system (CNS) is of utmost importance. Our study centers around the anatomical changes that occur after peripheral nerve injury in the rat spinal cord, namely the degradation of Ia input defined by the expression of the vesicular glutamate transporter 1 (VGLUT1). This study is based on the proposed microglia-dependent mechanism of permanent synaptic loss from the Rotterman et al. (2019) paper. We ask if 1) we can suppress microglia accumulation with minocycline, a tetracycline antibiotic, and 2) if using minocycline can help preserve the Ia sensory afferent synapses after nerve injury. We first retrogradely labeled the medial gastrocnemius motor pool in 15 adult Wistar rats. One week later, we transected the medial gastrocnemius nerve in the left hindlimb. Rats were either treated with vehicle or minocycline for 14 days following injury. Control animals were also produced. At 14 days post injury, animals were perfused, spinal cords were collected and subsequently sectioned. Using immunohistochemistry (IHC), we labeled VGLUT1 synapses on these injured motor neurons and imaged them with confocal microscopy for subsequent reconstruction and analysis. We found four main results: 1) treatment with minocycline for 14 days after nerve injury does not seem to prevent microglia proliferation, 2) the chromalytic reaction (somatic expansion) that commonly occurs after axotomy did not seem to occur in the minocycline- treated animals, 3) there was partial preservation of somatic VGLUT1 synapses in the minocycline-treatment animals, and 4) there was complete dendritic VGLUT1 synapse preservation in the minocycline-treated animals. Although there were limitations to the study with regards to the methods of counting microglia, the study produced robust conclusions that will aid in the development of further research. Future studies should be conducted on the efficacy of minocycline preserving the synapses, the molecular mechanisms underlying minocycline’s effects, and the potential recovery of nerve function.
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Date Issued
2022-05
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Text
Resource Subtype
Undergraduate Thesis