Poster, Podium & Video Sessions
Presentation Authors: Nobutaka Shimizu*, Shun Takai, Naoki Wada, Takahisa Suzuki, Ei-ichiro Takaoka, Takahiro Shimizu, Pittsburgh, PA, Akihide Hirayama, Nara, Japan, Hirotsugu Uemura, Osaka sayama, Japan, Anthony J. Kanai, Naoki Yoshimura, Pittsburgh, PA
Introduction: NGF is reportedly involved in changes in C-fiber bladder afferent pathways to induce detrusor overactivity (DO) following SCI. The expression of TRP channels such as TRPV1 and TRPA1 are known to be involved in sensitization of C-fiber afferent pathways. Also, TRPC channels such as TRPC1, TRPC3 and TRPC6 are shown to be expressed in dorsal root ganglia (DRG) although their roles in the control of bladder afferent function have not been well clarified. Therefore, we investigated the effects of anti-NGF antibody treatment on TRP channel expression in laser-captured bladder afferent neurons using SCI mice.
Methods: SCI was produced by Th8/9 spinal cord transection in female C57BL/6N mice. Two weeks later, an osmotic pump was placed subcutaneously to administer vehicle in spinal intact (SI), vehicle in SCI and 10µg/kg/hr of anti-NGF antibody in SCI mice for two weeks. Four weeks after SCI, L6 DRG were removed bilaterally, and gene expression of TRPA1, TRPV1, TRPC1, TRPC3 and TRPC6 was analyzed by real-time PCR in bladder afferent neurons which were labeled by Fast Blue injected into the bladder wall one week earlier and collected by laser-capture microdissection from L6 DRG sections.
Results: The mRNA expression of TRPV1, but not TRPA1, increased in vehicle-SCI mice compared to SI mice. The expressions of TRPC3 and TRPC6 in vehicle-SCI mice decreased compared to SI. However, in SCI mice treated with anti-NGF antibody, the mRNA expression of TRPV1 decreased and the mRNA levels of TRPC3 and TRPC6 increased compared to vehicle-SCI mice (Figure).
Conclusions: The anti-NGF antibody treatment reversed the changes in expressions of TRPV1 and TRPC3/TRPC6 which increased and decreased, respectively, after SCI in the mouse model. These results suggest that the NGF-dependent changes in specific genes such as TRPV1, TRPC3 and TRPC6 could be involved in SCI-induced DO, and that TRPC3/TRPC6 might have an inhibitory role in the control of bladder afferent activity while TRPV1 overexpression is involved in C-fiber sensitization to induce DO after SCI. These findings help to understand the TRP-mediated mechanism underlying neurogenic lower urinary tract dysfunction.
Source Of Funding: NIH P01 DK093424