Dataset Information

Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach.

ABSTRACT: Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach.DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension.Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89.Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.

SUBMITTER: Li M

PROVIDER: S-EPMC5503297 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Collateral branches from axons are key components of functional neural circuits that allow neurons to connect with multiple synaptic targets. Like axon growth and guidance, formation of collateral branches depends on the regulation of microtubules, but how such regulation is coordinated to ensure proper circuit development is not known. Based on microarray analysis, we have identified a role for microtubule-associated protein 7 (MAP7) during collateral branch development of dorsal root ganglion (DRG) sensory neurons. We show that MAP7 is expressed at the onset of collateral branch formation. Perturbation of its expression by overexpression or shRNA knockdown alters axon branching in cultured DRG neurons. Localization and time-lapse imaging analysis reveals that MAP7 is enriched at branch points and colocalizes with stable microtubules, but enters the new branch with a delay, suggesting a role in branch maturation. We have also investigated a spontaneous mutant mouse that expresses a truncated MAP7 and found a gain-of-function phenotype both in vitro and in vivo Further domain analysis suggests that the amino half of MAP7 is responsible for branch formation, suggesting a mechanism that is independent of its known interaction with kinesin. Moreover, this mouse exhibits increased pain sensitivity, a phenotype that is consistent with increased collateral branch formation. Therefore, our study not only uncovers the first neuronal function of MAP7, but also demonstrates the importance of proper microtubule regulation in neural circuit development. Furthermore, our data provide new insights into microtubule regulation during axonal morphogenesis and may shed light on MAP7 function in neurological disorders.SIGNIFICANCE STATEMENT Neurons communicate with multiple targets by forming axonal branches. In search of intrinsic factors that control collateral branch development, we identified a role for microtubule-associated protein 7 (MAP7) in dorsal root ganglion sensory neurons. We show that MAP7 expression is developmentally regulated and perturbation of this expression alters branch formation. Cell biological analysis indicates that MAP7 promotes branch maturation. Analysis of a spontaneous mouse mutant suggests a molecular mechanism for branch regulation and the potential influence of collateral branches on pain sensitivity. Our studies thus establish the first neuronal function of MAP7 and demonstrate its role in branch morphogenesis and neural circuit function. These findings may help in our understanding of the contribution of MAP7 to neurological disorders and nerve regeneration.

Dataset Information

Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets