Abstract
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated in various neurons and glial cells in the nervous system. Schwann cells (SCs) are primary glia cells that wrap around axons to form the myelin sheath in the peripheral nervous system. However, whether TRPV4 is expressed and functions in SCs is unclear. Here, we demonstrate functional expression of TRPV4 in mouse SCs and investigated its physiological significance. Deletion of TRPV4 did not affect normal myelin development for SCs in sciatic nerves in mice. However, after sciatic nerve cut injury, TRPV4 expression levels were remarkably increased in SCs following nerve demyelination. Ablation of TRPV4 expression impaired the demyelinating process after nerve injury, resulting in delayed remyelination and functional recovery of sciatic nerves. These results suggest that local activation of TRPV4 could be an attractive pharmacological target for therapeutic intervention after peripheral nerve injury.
Highlights
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated in various neurons and glial cells in the nervous system
These results indicated that TRPV4 is expressed in cultured Schwann cells (SCs)
TRPV4 channels are activated in nonmyelinating SCs at body temperature and nerve demyelination is enhanced
Summary
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated in various neurons and glial cells in the nervous system. After sciatic nerve cut injury, TRPV4 expression levels were remarkably increased in SCs following nerve demyelination. Ablation of TRPV4 expression impaired the demyelinating process after nerve injury, resulting in delayed remyelination and functional recovery of sciatic nerves. These results suggest that local activation of TRPV4 could be an attractive pharmacological target for therapeutic intervention after peripheral nerve injury. In the peripheral nervous system (PNS), myelin sheaths are formed by Schwann cells (SCs), which provide support and insulation to axons to facilitate rapid saltatory impulse conduction. A core set of transcription factors and signaling molecules are involved in SC differentiation during myelin development and remyelination following injury. Purinergic signaling plays a critical role in cytosolic Ca2+dependent SC differentiation[15] and proper myelin formation[18]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have