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Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat.

Xia CM, Gulick MA, Yu SJ, Grider JR, Murthy KS, Kuemmerle JF, Akbarali HI, Qiao LY - J Neuroinflammation (2012)

Bottom Line: Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus.However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided.Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Virginia Commonwealth University School of Medicine, 1220 East Broad Street, PO Box 0551, MMRB 5038, VA 23219 Richmond, Virginia, USA.

ABSTRACT

Background: In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.

Methods: Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.

Results: At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p < 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.

Conclusion: Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

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Prolonged pre-treatment with RTX blocked BDNF expression in L1 DRG during colonic inflammation. In vehicle-treated animals, colonic inflammation increased the level of BDNF in the L1 DRG at 3 days post TNBS treatment (A, B, E). Following prolonged RTX pre-treatment, the level of BDNF in L1 DRG from the inflamed animals was attenuated to almost normal level (D, E). Bar = 40 μm, *, p < 0.05 vs. control; #, p < 0.05 vs. TNBS-treated. n = 4 animals for each experimental group.
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Figure 5: Prolonged pre-treatment with RTX blocked BDNF expression in L1 DRG during colonic inflammation. In vehicle-treated animals, colonic inflammation increased the level of BDNF in the L1 DRG at 3 days post TNBS treatment (A, B, E). Following prolonged RTX pre-treatment, the level of BDNF in L1 DRG from the inflamed animals was attenuated to almost normal level (D, E). Bar = 40 μm, *, p < 0.05 vs. control; #, p < 0.05 vs. TNBS-treated. n = 4 animals for each experimental group.

Mentions: To examine if the activation of TRPV1 primary afferents (presumably C-fibers) had a role in BDNF up-regulation in sensory neurons during colonic inflammation, we determined the level of BDNF in animals treated with vehicle (10% Tween-80, 10% ethanol, and normal saline) + 50% EtOH (Figure 5A), vehicle + TNBS (Figure 5B), RTX + EtOH (Figure 5C), or RTX + TNBS (Figure 5D). Animals were pre-treated with either vehicle or RTX for one week and then were treated with either EtOH or TNBS for 3 days. The BDNF expression was examined by immunohistochemistry. Results showed that prolonged pre-treatment with RTX significantly attenuated colonic inflammation-induced BDNF up-regulation examined in L1 DRG (Figure 5E). RTX had no effects on the expression level of BDNF in DRG from non-inflamed animals (Figure 5E).


Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat.

Xia CM, Gulick MA, Yu SJ, Grider JR, Murthy KS, Kuemmerle JF, Akbarali HI, Qiao LY - J Neuroinflammation (2012)

Prolonged pre-treatment with RTX blocked BDNF expression in L1 DRG during colonic inflammation. In vehicle-treated animals, colonic inflammation increased the level of BDNF in the L1 DRG at 3 days post TNBS treatment (A, B, E). Following prolonged RTX pre-treatment, the level of BDNF in L1 DRG from the inflamed animals was attenuated to almost normal level (D, E). Bar = 40 μm, *, p < 0.05 vs. control; #, p < 0.05 vs. TNBS-treated. n = 4 animals for each experimental group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298724&req=5

Figure 5: Prolonged pre-treatment with RTX blocked BDNF expression in L1 DRG during colonic inflammation. In vehicle-treated animals, colonic inflammation increased the level of BDNF in the L1 DRG at 3 days post TNBS treatment (A, B, E). Following prolonged RTX pre-treatment, the level of BDNF in L1 DRG from the inflamed animals was attenuated to almost normal level (D, E). Bar = 40 μm, *, p < 0.05 vs. control; #, p < 0.05 vs. TNBS-treated. n = 4 animals for each experimental group.
Mentions: To examine if the activation of TRPV1 primary afferents (presumably C-fibers) had a role in BDNF up-regulation in sensory neurons during colonic inflammation, we determined the level of BDNF in animals treated with vehicle (10% Tween-80, 10% ethanol, and normal saline) + 50% EtOH (Figure 5A), vehicle + TNBS (Figure 5B), RTX + EtOH (Figure 5C), or RTX + TNBS (Figure 5D). Animals were pre-treated with either vehicle or RTX for one week and then were treated with either EtOH or TNBS for 3 days. The BDNF expression was examined by immunohistochemistry. Results showed that prolonged pre-treatment with RTX significantly attenuated colonic inflammation-induced BDNF up-regulation examined in L1 DRG (Figure 5E). RTX had no effects on the expression level of BDNF in DRG from non-inflamed animals (Figure 5E).

Bottom Line: Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus.However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided.Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Virginia Commonwealth University School of Medicine, 1220 East Broad Street, PO Box 0551, MMRB 5038, VA 23219 Richmond, Virginia, USA.

ABSTRACT

Background: In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.

Methods: Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.

Results: At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p < 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.

Conclusion: Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

Show MeSH
Related in: MedlinePlus