Role of LAR phosphatase in restricting axon regeneration after spinal cord injury

A poster of interest at the Society of Neuroscience 2013.

Program#/Poster#: 341.24/AA11

Presentation Title: Role of LAR phosphatase in restricting axon regeneration after spinal cord injury

Topic: ++C.11.d. Spinal cord: Cellular and molecular mechanisms

Authors: P. ABDUL-MUNEER1, H. LI1, Y. OHTAKE1, D. PARK1, F. LONGO3, *S. LI2;
2Shriners Hosp. Pediatric Res. Ctr., 1Temple Univ. Sch. of Med., Philadelphia, PA; 3Stanford Univ. Sch. of Med., Stanford, CA

Abstract: Extracellular matrix molecule chondroitin sulfate proteoglycans (CSPGs) are highly upregulated in the scar tissues after CNS injury and form a potent chemical barrier for axonal regeneration. Recent studies support that the receptor protein tyrosine phosphatase σ and leukocyte common antigen related (LAR) phosphatase mediate CSPG inhibition as functional receptors. Our lab shows that LAR binds CSPGs with high affinity and partially mediates the inhibition of neuronal growth by CSPGs (J Neurosc, 201; 31:14051-66). We find that the intracellular signaling Erk mediates CSPG-LAR interaction in vitro in addition to RhoA and Akt. After spinal cord injury (SCI), LAR protein was upregulated in the rostral spinal cord days to several weeks after a dorsal over-hemisection SCI in mice. To confirm the role of LAR in limiting axon growth in vivo, we examined the growth of descending axonal tracts in adult LAR mutant mice following a dorsal transection at T7. We found that LAR deletion increased the number of 5-HT-stained serotonin axons in the reactive scar tissues around the lesion and in the caudal spinal cord. Quantification of 5-HT fibers in transverse spinal cord sections 5-7 mm caudal to the lesion also indicates a greater number of 5-HT axons in LAR-deleted mice. Furthermore, we investigated the growth of corticospinal tract (CST) fibers and detected significantly enhanced numbers of CST axons in the scar tissues and the spinal cord several mm caudal to the lesion. Behavioral tests demonstrate increased BMS locomotor scores and reduced grid walk errors of the hindlimbs in LAR -/- mice several weeks after SCI. Together, our findings support the crucial role of LAR in restricting axon regrowth after CNS injury.


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