Abstract
Due to the microenvironment created by Schwann cell (SC) activity, peripheral nerve fibers are able to regenerate. Inflammation is the first response to nerve damage and the removal of cellular and myelin debris is essential in preventing the persistence of the local inflammation that may negatively affect nerve regeneration. Acetylcholine (ACh) is one of the neurotransmitters involved in the modulation of inflammation through the activity of its receptors, belonging to both the muscarinic and nicotinic classes. In this report, we evaluated the expression of α7 nicotinic acetylcholine receptors (nAChRs) in rat sciatic nerve, particularly in SCs, after peripheral nerve injury. α7 nAChRs are absent in sciatic nerve immediately after dissection, but their expression is significantly enhanced in SCs after 24 h in cultured sciatic nerve segments or in the presence of the proinflammatory neuropeptide Bradykinin (BK). Moreover, we found that activation of α7 nAChRs with the selective partial agonist ICH3 causes a decreased expression of c-Jun and an upregulation of uPA, MMP2 and MMP9 activity. In addition, ICH3 treatment inhibits IL-6 transcript level expression as well as the cytokine release. These results suggest that ACh, probably released from regenerating axons or by SC themselves, may actively promote through α7 nAChRs activation an anti-inflammatory microenvironment that contributes to better improving the peripheral nerve regeneration.
Highlights
During nerve repair, Schwann cells (SCs) and macrophages play essential roles in tissue homeostasis, promoting nerve regeneration [1,2,3,4]
Based on the anti-inflammatory properties associated to the α7 nicotinic acetylcholine receptors (nAChRs) [14,15], we investigated a potential contribution of this receptor subtype to nerve repair following peripheral injury
We assessed the expression of the α7 nAChR in Schwann cells after peripheral nerve injury and proved that the selective activation of this receptor subtype may be relevant to the establishment of the microenvironment favorable to improving nerve regeneration
Summary
Schwann cells (SCs) and macrophages play essential roles in tissue homeostasis, promoting nerve regeneration [1,2,3,4]. Previous studies demonstrated that different neurotransmitters may control and modulate a variety of biological processes during development as well as adult life physiology [5,6,7]. The selective activation of specific mAChRs, such as the M2 subtype, regulates some aspects of the SCs development [8,9,10,11] as well as those mechanisms aimed at enhancing their regenerative capability, modulating the production and release of the nerve growth factor (NGF) [12]. In several different districts, the cholinergic signal is mediated by activation of the composite family of nicotinic acetylcholine receptors (nAChRs). Based on the anti-inflammatory properties associated to the α7 nAChR [14,15], we investigated a potential contribution of this receptor subtype to nerve repair following peripheral injury
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