Poster abstracts
Poster number 92 submitted by Christopher Wier
AAV9-HSPB1: a novel tool for accelerating motor unit repair following peripheral nerve injury
Christopher G. Wier (Neuroscience), Lisa N. Miller (Biomedical Engineering, OSU), Patrick L. Heilman (Molecular & Cellular Biochemistry, OSU), Xueqian Wang (Molecular & Cellular Biochemistry, OSU), W. David Arnold (Neurology, Physical Medicine and Rehabilitation, Neuroscience, OSU), Stephen J. Kolb (Neurology, Molecular & Cellular Biochemistry, OSU)
Abstract:
The motor unit is made up of a motor neuron and all muscle fibers that receive its innervation. Improving motor unit repair following a denervating injury or disease is a crucial research area to ensure return of muscle function. The small heat shock protein B1 (HspB1) is a promising candidate for accelerating motor unit repair and recovering muscle function. HSPB1 expression increases in motor neurons and glial cells following neuronal injury and transgenic lines overexpressing the protein result in accelerated axonal growth [1-3]. We have built off our prior work involving self-complementary adeno-associated virus serotype 9 (scAAV9) to develop a tool for targeting HSPB1 overexpression in motor neurons and astrocytes, AAV9-HSPB1. A longitudinal motor unit repair time course has been produced in mice with a sciatic nerve crush using a combination of compound muscle action potential (CMAP) and motor unit number estimate (MUNE) measurements—recordings performed by clinicians on patients with peripheral nerve injury—and paw print measurements. We have demonstrated accelerated motor unit repair in mice injected with AAV9-HSPB1 compared to non-injected mice, with CMAP and MUNE returning to pre-crush levels by 42 days post injury (dpi) versus approximately 80dpi.
References:
1. Costigan, M., et al., Heat shock protein 27: developmental regulation and expression after peripheral nerve injury. J Neurosci, 1998. 18(15): p. 5891-900.
2. Benn, S.C., et al., Hsp27 upregulation and phosphorylation is required for injured sensory and motor neuron survival. Neuron, 2002. 36(1): p. 45-56.
3. Ma, C.H., et al., Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice. J Clin Invest, 2011. 121(11): p. 4332-47.
Keywords: scAAV9, HSPB1, Motor unit repair