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- Title
Herpes simplex virus vector-mediated gene transfer of kynurenine aminotransferase improves detrusor overactivity in spinal cord-injured rats.
- Authors
Jia, C; Yoshimura, N; Liao, L
- Abstract
Detrusor overactivity threatens the renal function of patients with spinal cord injury. Suppressing N-methyl-D-aspartate receptors is known to improve detrusor overactivity in rats with spinal cord injury, whereas kynurenic acid, the endogenous antagonist of N-methyl-D-aspartate receptors, is irreversibly synthesized by kynurenine aminotransferases (KATs). In this study, we investigated whether replication-defective herpes simplex virus vector-mediated gene transfer of human KAT II could treat detrusor overactivity by injecting the vectors into the rat bladder wall 1 week after spinal cord injury. Three weeks after injection, we evaluated the cystometry and gene expression of KAT II in L6-S1 dorsal root ganglia. The results showed that the vectors are transported to L6-S1 dorsal root ganglia and upregulate the expression of KAT II, and that they also improve the detrusor overactivity and voiding efficiency. We also proved that N-methyl-D-aspartate receptors were blocked by kynurenic acid in the extracellular solution or the vector-mediated gene transfer of KAT II in cultured rat neurons of L6-S1 dorsal root ganglia by whole-cell patch clamp to explore the mechanisms of gene therapy. Therefore, replication-defective herpes simplex virus vector-mediated KAT II inhibits detrusor overactivity in spinal cord-injured rats, possibly by suppressing N-methyl-D-aspartate receptors in bladder afferent pathways.
- Subjects
HERPES simplex virus; GENETIC transformation; SPINAL cord injuries; THERAPEUTICS; KYNURENINE; AMINOTRANSFERASE genetics; HYPERKINESIA; LABORATORY rats; PATIENTS with spinal cord injuries
- Publication
Gene Therapy, 2014, Vol 21, Issue 5, p484
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2014.19