Dataset Information

Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves.

ABSTRACT: Glucose-responsive ATP-sensitive potassium channels (K_ATP) are expressed in a variety of tissues including nervous systems. The depolarization of the membrane potential induced by glucose may lead to hyperexcitability of neurons and induce excitotoxicity. However, the roles of K_ATP in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of K_ATP in the PNS using K_ATP-deficient (Kir6.2-deficient) mice. We demonstrate that neurite outgrowth of dorsal root ganglion (DRG) neurons was reduced by channel closers sulfonylureas. However, a channel opener diazoxide elongated the neurite. K_ATP subunits were expressed in mouse DRG, and expression of certain subunits including Kir6.2 was increased in diabetic mice. In Kir6.2-deficient mice, the current perception threshold, thermal perception threshold, and sensory nerve conduction velocity were impaired. Electron microscopy revealed a reduction of unmyelinated and small myelinated fibers in the sural nerves. In conclusion, K_ATP may contribute to the development of peripheral neuropathy.

SUBMITTER: Nakai-Shimoda H

PROVIDER: S-EPMC8719014 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves.

Nakai-Shimoda Hiromi H Himeno Tatsuhito T Okawa Tetsuji T Miura-Yura Emiri E Sasajima Sachiko S Kato Makoto M Yamada Yuichiro Y Morishita Yoshiaki Y Tsunekawa Shin S Kato Yoshiro Y Seino Yusuke Y Inoue Rieko R Kondo Masaki M Seino Susumu S Naruse Keiko K Kato Koichi K Mizukami Hiroki H Nakamura Jiro J Kamiya Hideki H

iScience 20211211 1

Glucose-responsive ATP-sensitive potassium channels (KATP) are expressed in a variety of tissues including nervous systems. The depolarization of the membrane potential induced by glucose may lead to hyperexcitability of neurons and induce excitotoxicity. However, the roles of KATP in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of KATP in the PNS using KATP-deficient (Kir6.2-deficient) mice. We demonst ...[more]

PMID: 35005553

Similar Datasets

Project description:BackgroundThe cuprizone (CPZ) model of multiple sclerosis (MS) was used to identify microRNAs (miRNAs) related to in vivo de- and remyelination. We further investigated the role of miR-146a in miR-146a-deficient (KO) mice: this miRNA is differentially expressed in MS lesions and promotes differentiation of oligodendrocyte precursor cells (OPCs) during remyelination, but its role has not been examined during demyelination.MethodsMicroRNAs were examined by Agilent Mouse miRNA Microarray in the corpus callosum during CPZ-induced demyelination and remyelination. Demyelination, axonal loss, changes in number of oligodendrocytes, OPCs, and macrophages/microglia was compared by histology/immunohistochemistry between KO and WT mice. Differential expression of target genes and proteins of miR-146a was analyzed in the transcriptome (4 × 44K Agilent Whole Mouse Genome Microarray) and proteome (liquid chromatography tandem mass spectrometry) of CPZ-induced de- and remyelination in WT mice. Levels of proinflammatory molecules in the corpus callosum were compared in WT versus KO mice by Meso Scale Discovery multiplex protein analysis.ResultsmiR-146a was increasingly upregulated during CPZ-induced de- and remyelination. The absence of miR-146a in KO mice protected against demyelination, axonal loss, body weight loss, and atrophy of thymus and spleen. The number of CNP+ oligodendrocytes was increased during demyelination in the miR-146a KO mice, while there was a trend of increased number of NG2+ OPCs in the WT mice. miR-146a target genes, SNAP25 and SMAD4, were downregulated in the proteome of demyelinating corpus callosum in WT mice. Higher levels of SNAP25 were measured by ELISA in the corpus callosum of miR-146a KO mice, but there was no difference between KO and WT mice during demyelination. Multiplex protein analysis of the corpus callosum lysate revealed upregulated TNF-RI, TNF-RII, and CCL2 in the WT mice in contrast to KO mice. The number of Mac3+ and Iba1+ macrophages/microglia was reduced in the demyelinating corpus callosum of the KO mice.ConclusionDuring demyelination, absence of miR-146a reduced inflammatory responses, demyelination, axonal loss, the number of infiltrating macrophages, and increased the number of myelinating oligodendrocytes. The number of OPCs was slightly higher in the WT mice during remyelination, indicating a complex role of miR-146a during in vivo de- and remyelination.

Dataset Information

Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves.

Publications

<i>Kir6.2</i>-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets