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TAC‐302 promotes neurite outgrowth of isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following bladder outlet obstruction in rats
Author(s) -
Yoshida Shohei,
Orimoto Naoki,
Tsukihara Hiroshi,
Noma Takahisa,
Hakozaki Atsushi,
Sasaki Eiji
Publication year - 2018
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.23375
Subject(s) - medicine , denervation , neurite , bladder outlet obstruction , urology , urinary bladder , cystometry , dorsal root ganglion , endocrinology , anatomy , dorsum , in vitro , chemistry , prostate , biochemistry , cancer
Aims To evaluate the ability of TAC‐302, a cyclohexenoic fatty alcohol derivative, to enhance neurite outgrowth in cultured rat dorsal root ganglion (DRG) neurons, and the preventive effects of TAC‐302 on bladder denervation‐related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO). Methods Rat DRG neurons were cultured in the presence of TAC‐302. Cell numbers and neurite lengths were quantified after a 24 h culture. BOO was achieved by partial ligature of the proximal urethra in female rats. BOO rats were divided into three groups and orally treated with vehicle of 3 or 30 mg/kg TAC‐302 twice a day for 4 weeks. Cystometry was performed under conscious conditions. Immunohistochemical staining using anti‐PGP9.5 of the bladder muscle layer was performed, and the innervation area was scored. Results TAC‐302 significantly and dose‐dependently increased neurite outgrowth in cultured DRG neurons. BOO rats showed a decreased innervation area in the urinary bladder compared to sham‐operated rats. BOO‐induced denervation of the urinary bladder was partially prevented by oral treatment with TAC‐302. TAC‐302 significantly reduced the frequency of non‐voiding contraction (NVC) and residual urine volume (RUV) compared with the BOO vehicle group ( P < 0.05). The innervation area score exhibited significant negative correlations with NVC and RUV, indicating that they increased according to the progression of denervation. Conclusions Our data indicate that TAC‐302 promotes neurite outgrowth in vitro. In addition, TAC‐302 prevents BOO‐induced bladder dysfunction in rats, and has a protective effect on bladder denervation.