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L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation.

ABSTRACT: L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (six segments; T10-L2) on both wild-type and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy.

SUBMITTER: Runyan SA

PROVIDER: S-EPMC2267744 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation.

Runyan S A SA Roy R R RR Zhong H H Phelps P E PE

Neuroscience 20071018 4

L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (six segments; T10-L2) on bot ...[more]

PMID: 18022323

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Project description:Primary afferent collateral sprouting (PACS) is a process whereby non-injured primary afferent neurons respond to some stimulus by extending new branches from existing axons. In the model used here (spared dermatome), the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity. Investigations of gene expression changes associated with PACS can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatment for spinal cord injury to promote functional recovery. In this study, we sought to identify gene expression changes in PACS using 20 Affymetrix Rat Genome 230 2.0 microarrays. The experiments were designed to discover global gene expression changes in non-injured DRG neurons undergoing PACS. T11 DRG neurons remained intact and undergo PACS after the cutaneous nerves of the adjacent segments (T9, T10, T12, and T13) were injured and regeneration of those injured nerves prevented by ligation. Thus, the T9, T10, T12, and T13 dermatomes were denervated, but the T11 dermatome remained intact. Axons of the T11dermatome (and thus housed in the T11 dorsal root ganglion (DRG)), extended new branches to innervate the T9, T10, T12, and T13 dermatomes. N.B.: This is NOT a spared root experiment. ALL spinal roots were non-injured. Peripheral nerves were used. A total of 20 Affymetrix Rat Genome 230 2.0 microarrays were analyzed: six naÃ¯ve controls, seven replicates at day 7 post-surgery (presumed to represent an â??initiation phaseâ??), and seven replicates at day 14 post-surgery (presumed to represent a â??maintenance phaseâ??). DRGs were NOT pooled onto microarrays. Each animal had its own microarray with T11 DRG sample which underwent 2-round amplification. After quality control analysis, one of the naÃ¯ve control microarrays was removed from further analysis.

Dataset Information

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation.

Publications

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation.

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