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Spinal cord injury (SCI) results in loss of sensory and motor function because injured axons do not regenerate and neurons that die are not replaced. Nevertheless, there is evidence for spontaneous reorganization of spared pathways (i.e. sprouting) that could be exploited to improve functional recovery. The extent of morphological remodeling after spinal cord injury is, however, not understood. We have previously shown that a phosphorylated form of microtubule-associated protein-1B, MAP1B-P, is expressed by growing axons, but is detected in intact adult SC in fibers exhibiting a somatotopic distribution of myelinated sensory fibers. We now demonstrate that after adult SCI, MAP1B-P is up-regulated in other classes of axons. We used immunohistochemistry to show changing levels and distributions of MAP1B-P after a right thoracic hemisection of adult rat spinal cord. MAP1B-P labeling suggests rearrangements of the axonal circuitry that go well beyond previous descriptions. MAP1B-P-positive fibers are present in ectopic locations in gray matter in both dorsal and ventral horns and around the central canal. Double staining reveals that primary sensory and descending serotonergic and corticospinal axons are MAP1B-P positive. In white matter, high MAP1B-P expression is found on terminal enlargements near the injury, reflecting retraction of transected axons. MAP1B-P also accumulates in pre-apoptotic neuronal somata axotomized by the lesion, indicating association of MAP1B-P not only with axon extension and retraction, but also with neuronal degeneration. Finally, we provide evidence that MAP1B phosphorylation is correlated with activation of JNK MAP-kinase, providing a step towards unraveling the mechanisms of regulation of this plasticity-related cytoskeletal protein.

A peripheral nerve lesion induces sprouting of primary afferents from dorsal root ganglion (DRG) neurons into lamina II of the dorsal horn. Modifications of the environment in consequence to the axotomy provide an extrinsic stimulus. A potential neuron-intrinsic factor that may permit axonal sprouting is microtubule-associated protein 1B (MAP1B) in a specific phosphorylated form (MAP1B-P), restricted to growing or regenerating axons. We show here that both in rat and mouse, a sciatic nerve cut is rapidly followed by the appearance of MAP1B-P expression in lamina II, increasing to a maximum between 8 and 15 days, and diminishing after three months. Evidence is provided that sprouting and induction of MAP1B-P expression after peripheral injury are phenomena concerning essentially myelinated axons. This is in accordance with in situ hybridization data showing especially high MAP1B-mRNA levels in large size DRG neurons that give rise to myelinated fibers. We then employed a second lesion model, multiple rhizotomy with one spared root. In this case, unmyelinated CGRP expressing fibers do indeed sprout, but coexpression of MAP1B-P and CGRP is never observed in lamina II. Finally, because a characteristic of myelinated fibers is their high content in neurofilament protein heavy subunit (NF-H), we used NF-H-LacZ transgenic mice to verify that MAP1B-P induction and central sprouting were not affected by perturbing the axonal organization of neurofilaments. We conclude that MAP1B-P is well suited as a rapidly expressed, axon-intrinsic marker associated with plasticity of myelinated fibers.