The receptor protein tyrosine phosphatase HmLAR1 is up-regulated in the CNS of the adult medicinal leech following injury and is required for neuronal sprouting and regeneration
Research article published in Molecular and cellular neurosciences (2010)
Abstract
LAR-like receptor protein tyrosine phosphatases (RPTPs), which are abundantly expressed in the nervous systems of most if not all bilaterian animals thus far examined, have been implicated in regulating a variety of critical neuronal processes. These include neuronal pathfinding, adhesion and synaptogenesis during development and, in adult mammals, neuronal regeneration. Here we explored a possible role of a LAR-like RPTP (HmLAR1) in response to mechanical trauma in the adult nervous system of the medicinal leech. In situ hybridization and QPCR analyses of HmLAR1 expression in individual segmental ganglia revealed a significant up-regulation in receptor expression following CNS injury, both in situ and following a period in vitro. Furthermore, we observed up-regulation in the expression of the leech homologue of the Abelson tyrosine kinase, a putative signaling partner to LAR receptors, but not among other tyrosine kinases. The effects on neuronal regeneration were assayed by comparing growth across a nerve crush by projections of individual dorsal P neurons (P(D)) following single-cell injection of interfering RNAs against the receptor or control RNAs. Receptor RNAi led to a significant reduction in HmLAR1 expression by the injected cells and resulted in a significant decrease in sprouting and regenerative growth at the crush site relative to controls. These studies extend the role of the HmLARs from leech neuronal development to adult neuronal regeneration and provide a platform to investigate neuronal regeneration and gene regulation at the single cell level.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Peer-reviewed clinical and outcomes research relevant to medicinal leech therapy and its biology. Indexed in PubMed and verified against the NCBI record.
Why This Matters for Hirudotherapy
Working directly in Hirudo medicinalis, this study found that the LAR-like receptor protein tyrosine phosphatase HmLAR1 is up-regulated in the adult medicinal-leech central nervous system after injury and is required for neuronal sprouting and regeneration: single-cell RNAi knockdown of HmLAR1 in identified P neurons significantly reduced sprouting and regenerative growth across a nerve crush versus controls, and the leech homologue of Abelson tyrosine kinase was also up-regulated. This matters because it uses the medicinal leech as a tractable model nervous system to dissect, at single-cell resolution, the molecular machinery of adult neuronal regeneration, the same well-mapped neurobiology that has made Hirudo a classic laboratory organism and that underpins scientific interest in the species beyond its anticoagulant secretome. As a caveat, this is preclinical, organism-level developmental neuroscience in the leech itself; it is unrelated to clinical hirudotherapy outcomes and says nothing about treating human disease.
Citation
The receptor protein tyrosine phosphatase HmLAR1 is up-regulated in the CNS of the adult medicinal leech following injury and is required for neuronal sprouting and regeneration.
Sethi J et al. · Molecular and cellular neurosciences, 2010
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