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-mediated colon-to-bladder sensory cross-activation involved the TrkB-PLCγ-calcium/calmodulin-dependent protein kinase II (CaMKII) cascade. In contrast, the PI3K/Akt pathway was not activated in bladder afferent neurons during colitis and was not involved in BDNF action in the DRG. Our results suggest that colon-to-bladder sensory cross-sensitization is regulated by specific signal transduction initiated by the up-regulation of BDNF in the DRG.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Xia C,Shen S,Hashmi F,Qiao LYdoi
10.1016/j.expneurol.2015.12.006subject
Has Abstractpub_date
2016-11-01 00:00:00pages
126-135issue
Pt Beissn
0014-4886issn
1090-2430pii
S0014-4886(15)30133-3journal_volume
285pub_type
杂志文章abstract::Estrogens and N-methyl-D-aspartate (NMDA) receptors regulate multiple aspects of morphological and functional plasticity in young animals. For example, estrogens increase spine density in the hippocampus, and NMDA antagonists block these effects. Few studies have examined the effects of age, postovariectomy interval, ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2001.7716
更新日期:2001-08-01 00:00:00
abstract::The present study evaluated the growth potential and differentiation of human fetal spinal cord (FSC) tissue in the injured adult rat spinal cord under different lesion and grafting conditions. Donor tissue at 6-9 weeks of gestational age was obtained through elective abortions and transplanted either immediately into...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6703
更新日期:1997-12-01 00:00:00
abstract::Polymerized collagen rolls enclosing Schwann cells (SCs) raised in culture were grafted into cystic cavities formed after lesioning the thoracic spinal cord of adult rats. Axons were already present within the graft by 14 days after implantation and both ensheathed and myelinated axons were numerous by 28 days. This a...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(91)90043-c
更新日期:1991-11-01 00:00:00
abstract::Massive increases in extracellular dopamine have been reported in the ischemic rodent striatum, implicating this neurotransmitter in toxic events. We have examined whether dopamine receptor antagonists are protective against hypoxic insult, using brain slices containing the rostral striatum obtained from adult male C5...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2002.7926
更新日期:2002-07-01 00:00:00
abstract::Huntington's disease is an autosomal dominant neurogenetic disorder leading to striatal atrophy, characterized by involuntary movements. Voluntary movements also deteriorate, but the neurophysiological mechanisms are less understood. We investigated voluntary movement execution and its neural correlates by means of mo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.11.018
更新日期:2009-03-01 00:00:00
abstract::We examined the effect of glial cell line-derived neurotrophic factor (GDNF) upon nigrostriatal dopaminergic function in response to two-pulse potassium (K(+)) stimulation in rats under in vivo microdialysis conditions. The two-pulse infusion protocol permits us to focus upon the role of this neurotrophin as related t...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7515
更新日期:2000-12-01 00:00:00
abstract::We have studied the functional involvement of J1-160 and J1-180 in the interaction between oligodendrocytes and neurons, astrocytes, or L cells in short- and long-term adhesion assays using monoclonal antibodies directed against topographically distinct epitopes on the molecules. Whereas antibodies to mouse liver memb...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(05)80012-3
更新日期:1990-07-01 00:00:00
abstract::Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulato...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.01.011
更新日期:2014-04-01 00:00:00
abstract::Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and pre...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113175
更新日期:2020-04-01 00:00:00
abstract::In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. ...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2012.01.010
更新日期:2013-08-01 00:00:00
abstract::Single-unit microelectrode studies were conducted to test the effects of systemic cocaine HCl on spontaneously firing single noradrenergic locus ceruleus (presynaptic) and cerebellar Purkinje (postsynaptic) neurons in rats in vivo. The spontaneous neuronal activity of all locus ceruleus neurons was inhibited by cocain...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90261-5
更新日期:1987-12-01 00:00:00
abstract::Exposure of the rodent striatum to quinolinic acid (QA, N-methyl-D-aspartate receptor agonist) induces immediate early gene (IEG; c-fos, c-jun, jun-B, zif/268) expression that may extend 12-24 h after injection. In order to determine the specificity of the prolonged IEG response to the QA injection, the temporal patte...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6427
更新日期:1997-04-01 00:00:00
abstract::Here, we describe a bilateral cervical contusion model for mice. Adult female mice received graded bilateral contusion injuries at cervical level 5 (C5) using a commercially available impactor (the IH device). Three separate experiments were carried out to define conditions that produce impairments in forelimb functio...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2009.09.028
更新日期:2010-01-01 00:00:00
abstract::Substantial progress has been made towards understanding the molecular basis for limited endogenous central nervous system (CNS) axonal growth after injuries such as spinal cord trauma. Realization of the potential benefit of therapeutic interventions requires methods to assess axonal growth and functional reorganizat...
journal_title:Experimental neurology
pub_type: 评论,杂志文章,评审
doi:10.1016/j.expneurol.2008.02.017
更新日期:2008-06-01 00:00:00
abstract::Sympathetic innervation of lymphoid tissues is localized to specific tissue compartments, but little is known of the "factors" that are important in establishing this pattern during development. Numerous studies have shown interactions of nerve growth factor (NGF) with the immune system, which may include modulation o...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6711
更新日期:1998-01-01 00:00:00
abstract::Paclitaxel is an effective chemotherapeutic agent that, despite its common use, often causes peripheral sensory neuropathy. In neurons, paclitaxel binds to and stabilizes microtubules, and through unknown mechanisms, bundles microtubules and disrupts their organization. Because microtubules serve as tracks on which a ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2015.06.023
更新日期:2015-09-01 00:00:00
abstract::One approach to repair of transected nerves is to attempt extrinsic guidance of axons across the gaps. We inserted the proximal and distal stumps of severed mouse sciatic nerves into opposite ends of biodegradable polyester tubes. The nerves and ensheathing tubes were examined after postoperative survival times of as ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90162-1
更新日期:1985-12-01 00:00:00
abstract::Relatively few behavioral deficits are apparent in subjects with hereditary absence of the corpus callosum (CC). The anterior commissure (AC) has been suggested to provide an extracallosal route for the transfer of interhemispheric information in subjects with this congenital defect. Anterior commissure size, axon num...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6564
更新日期:1997-08-01 00:00:00
abstract::We assessed the potential of different MRI measures to detect and quantify skeletal muscle changes with denervation in two mouse models of denervation/neurogenic atrophy. Acute complete denervation and chronic partial denervation were examined in calf muscles after sciatic nerve axotomy and in transgenic SOD1(G93A) mi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.04.033
更新日期:2008-08-01 00:00:00
abstract::Although axons lose some of their intrinsic capacity for growth after their developmental period, some axons retain the potential for regrowth after injury. When provided with a growth-promoting substrate such as a peripheral nerve graft (PNG), severed axons regenerate into and through the graft; however, they stop wh...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2012.09.011
更新日期:2013-01-01 00:00:00
abstract::The role of type IIA receptor protein tyrosine phosphatases (RPTPs), which includes LAR, RPTPσ and RPTPδ, in the nervous system is becoming increasingly recognized. Evidence supports a significant role for these RPTPs during the development of the nervous system as well as after injury, and mutations in RPTPs are asso...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.02.007
更新日期:2014-05-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative syndrome characterized by the systemic loss of motor neurons with prominent astrocytosis and microgliosis in the spinal cord and brain. Astrocytes play an essential role in maintaining extracellular microenvironments that surround motor neu...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2018.06.009
更新日期:2018-09-01 00:00:00
abstract::Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. Th...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.03.002
更新日期:2017-06-01 00:00:00
abstract::The nontoxic C fragment of tetanus toxin (TC) can transport other proteins from the circulation to central nervous system (CNS) motor neurons. Increased levels of CuZn superoxide dismutase (SOD) are protective in experimental models of stroke and Parkinson's disease, whereas mutations in SOD can cause motor neuron dis...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6490
更新日期:1997-06-01 00:00:00
abstract::Cannabis abuse may precipitate the onset of schizophrenia and a dysfunction of the endocannabinoid system may be involved in the pathology of schizophrenia. Nevertheless, only few studies have addressed the neurobiological consequences of cannabis abuse for the development and course of schizophrenia. We measured the ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.02.004
更新日期:2007-05-01 00:00:00
abstract::The cellular events in traumatic brain injury (TBI) are complicated, and the factors mediating neurotrophins to protect and repair the injured brain cells are only beginning to be identified. This study examined the effect of dexamethasone (DEX) on neurotrophin-3 (NT-3) expression following TBI. Levels of NT-3 mRNA an...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.12.023
更新日期:2005-04-01 00:00:00
abstract::Neurosphere-forming cells (NSFCs) derived from primary cultures of adult human olfactory epithelium were established in minimum essential medium (MEM) with Hanks balanced salts and 10% heat-inactivated fetal bovine serum (FBS). A totally defined medium (DM) was employed to examine their proliferation, lineage restrict...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2003.10.022
更新日期:2004-04-01 00:00:00
abstract::We have previously found that fetal cortex taken from 16- to 18-day-old donors survives grafting to the infarcted cortex 5-7 days after middle cerebral artery occlusion. The present study was undertaken to examine the effect on graft survival of varying the age of the fetal donor tissue and the time between vessel occ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1086
更新日期:1994-05-01 00:00:00
abstract::Spinal cord injury (SCI) initiates biochemical events that lead to an increase in extracellular excitatory amino acid concentrations, resulting in glutamate receptor-mediated excitotoxic events. These receptors include the three groups of metabotropic glutamate receptors (mGluRs). Group I mGluR activation can initiate...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2001.7721
更新日期:2001-08-01 00:00:00
abstract::Following a traumatic brain injury (TBI), the excessive release of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) is a major cause of cerebral edema, which, in turn, can cause permanent neuronal loss and cognitive deficits in laboratory rats. This study examined the changes in expression of t...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.06.008
更新日期:2004-10-01 00:00:00