Examination of the Effect of Minocycline Administration on Nerve Reinnervation in Rat Muscle Tissue After Nerve Injury
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Amosu, Oreoluwa Oladunni
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Abstract
Peripheral nerve injury leads to a loss of connection between the neural circuits in the central nervous system and the musculoskeletal system, and most patients have poor functional outcomes following peripheral nerve injury and never regain normal function (Zhang et al. 2022). Due to this, it is crucial to investigate the effects of peripheral nerve injury and explore avenues to improve outcomes following peripheral nerve injury. Our study is centered on investigating the impact of minocycline, a tetracycline antibiotic, on peripheral nerve regeneration following injury. When minocycline is delivered systemically, a generalized suppression of inflammation occurs throughout the body. We aim to discover 1) if minocycline administration influences the anatomical extent of peripheral nerve regeneration after injury and 2) if minocycline administration decreases the efficacy of peripheral nerve axon regeneration by disrupting a necessary pro-inflammatory response that occurs after nerve injury. We first transected the peripheral nerve supply to the medial gastrocnemius (MG) muscle of 17 Wistar rats via a surgical procedure. After nerve injury, we then categorized the animals into ones treated with minocycline or vehicle. Control animals that were not nerve-injured were also utilized. Rats in the minocycline condition were administered 35 mg of minocycline once daily for 14 days immediately following nerve injury via food cubes Rats in the vehicle condition did not receive minocycline via the food cubes administered to them. Tissue from the animals was then collected at 0 days (control), 14 days, and between a 6-12 month time period. The collected tissue was then sectioned, and immunohistochemistry (IHC) was used to label the nicotinic receptors at the postsynaptic side of the neuromuscular junctions (NMJs) and the motor axons innervating the NMJs. Heavy chain neurofilament (NFH) was also utilized during IHC to label the presynaptic side of the NMJs. After IHC, the tissue sections were then imaged with confocal microscopy and analyzed. We found that minocycline administration did not significantly impact nerve degeneration or regeneration. Future studies should be conducted on how minocycline anatomically impacts the reinnervation of sensory neurons, as well as the reinnervation of muscle spindles by Ia and group II afferents.
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Undergraduate Research Option Thesis