Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLC γ pathway.

Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway.
Exp Neurol. 2016 Nov;285(Pt B):126-135
Authors: Xia C, Shen S, Hashmi F, Qiao LY
Abstract
Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often experience increased sensory responsiveness in the urinary bladder reflecting neurogenic bladder overactivity. Here we demonstrate that colitis-induced up-regulation of the phospholipase C gamma (PLCγ) pathway downstream of brain-derived neurotrophic factor (BDNF) in bladder afferent neurons in the dorsal root ganglia (DRG) plays essential roles in activating these neurons thereby leading to bladder hyperactivity. Upon induction of colitis with 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats, we found that the phosphorylation (activation) level of cAMP responsive element-binding (p-CREB) protein, a molecular switch of neuronal plasticity, was increased in specifically labeled bladder afferent neurons in the thoracolumbar and lumbosacral DRGs. In rats having reduced levels of BDNF (BDNF(+/-)), colitis failed to elevate CREB protein activity in bladder afferent neurons. Physiological examination also demonstrated that colitis-induced urinary frequency was not shown in BDNF(+/-) rats, implicating an essential role of BDNF in mediating colon-to-bladder sensory cross-sensitization. We further implemented in vivo and in vitro studies and demonstrated that BDNF-mediate...

Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Xia C, Shen S, Hashmi F, Qiao LY Tags: Exp Neurol Source Type: research