Disrupting protein tyrosine phosphatase σ does not prevent sympathetic axonal dieback following myocardial infarction.

Abstract

The neuronal receptor protein tyrosine phosphatase receptor σ (PTPσ) inhibits axonal extension upon binding to chondroitin sulfate proteoglycans (CSPGs) in scar tissue. We recently demonstrated that modulating or deleting PTPσ promoted re-innervation of the CSPG-containing cardiac scar after ischemia-reperfusion (I-R). However, it remains unknown if the lack of PTPσ or early treatment with the PTPσ modulator, intracellular sigma peptide (ISP), prevents the initial injury-induced axonal dieback. To address this, we carried out I-R in PTPσ -/- mice or control littermates treated with ISP or vehicle immediately at the time of I-R, and then assessed sympathetic innervation of the scar and surrounding myocardium 3days later. Vehicle-treated WT controls displayed sympathetic denervation within the scar and viable tissue adjacent to the scar, as well as distal myocardium farther from the scar. PTPσ -/- and ISP-treated animals also displayed denervation of the scar and adjacent tissue, but regions distal to the scar were innervated normally. This suggests that PTPσ does not mediate axonal dieback but its disruption enhances axonal regrowth in the heart. CSPG digestion alters the macrophage response to prevent axonal dieback in spinal neurons, so we investigated whether targeting PTPσ might alter the macrophage response in the heart. The macrophage response after I-R was similar in vehicle and ISP-treated groups. Mice lacking PTPσ trended toward an increased M2 response, but were not significantly different than the other groups. These data suggest that PTPσ is not involved in axonal dieback or the early macrophage response following cardiac I-R.

• Authors: Dustin Johnsen, Antoinette Olivas, Bradley Lang, Jerry Silver, Beth Habecker
• Journal: Experimental neurology (Exp Neurol) Vol. 276 Pg. 1-4 (Feb 2016) ISSN: 1090-2430 [Electronic] United States
• PMID: 26616238 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• PTPRD protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 2

Topics

• Animals
• Axons (enzymology, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Mice, Transgenic
• Myocardial Infarction (enzymology, genetics, pathology)
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (deficiency, genetics)