RGD Reference Report - Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats. - Rat Genome Database

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Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats.

Authors: Yoshimura, N  Bennett, NE  Hayashi, Y  Ogawa, T  Nishizawa, O  Chancellor, MB  De Groat, WC  Seki, S 
Citation: Yoshimura N, etal., J Neurosci. 2006 Oct 18;26(42):10847-55.
RGD ID: 7242798
Pubmed: (View Article at PubMed) PMID:17050722
DOI: Full-text: DOI:10.1523/JNEUROSCI.3023-06.2006

Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 microg/microl) was infused continuously into the intrathecal space at the L6-S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 microl/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6-S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Ngf  (nerve growth factor)

Genes (Mus musculus)
Ngf  (nerve growth factor)

Genes (Homo sapiens)
NGF  (nerve growth factor)

Additional Information