Dorsal root ganglia CSF1 neuronal subtypes have different impact on macrophages and microglia after spared nerve injury.

Background And Aims: Colony-stimulating factor 1 (CSF1) is a growth factor secreted by dorsal root ganglia (DRG) neurons important for DRG macrophages and spinal cord (SC) microglia injury-induced proliferation and activation, specifically released after spared nerve injury (SNI). In this study, we investigated if SNI-induced CSF1 expression and perineuronal rings of macrophages around mouse DRG neurons vary between L3-L5 DRG and with the neuronal type, and if the CSF1 neuronal projections at the SC dorsal horns were associated with an increased microglial number in the corresponding laminae.

Methods: Seven days after surgery, L3-L5 DRG as well as their corresponding segments at the SC level were collected, frozen, and cut.

Electrophysiological properties of dorsal root ganglion neurons cultured on 3D silicon micro-pillar substrates.

Background: Silicon-based micro-pillar substrates (MPS), as three-dimensional cell culture platforms with vertically aligned micro-patterned scaffolding structures, are known to facilitate high-quality growth and morphology of dorsal root ganglion (DRG) sensory neurons, promote neurite outgrowth and enhance neurite alignment. However, the electrophysiological aspects of DRG neurons cultured on silicon MPSs have not been thoroughly investigated, which is of greatest importance to ensure that such substrates do not disrupt neuronal homeostasis and function before their widespread adoption in diverse biomedical applications.

New Method: We conducted whole-cell patch-clamp recordings to explore the electrophysiological properties of DRG neurons cultured on MPS arrays, utilizing a custom-made upright patch-clamp setup.

Potassium channel modulation in macrophages sensitizes dorsal root ganglion neurons after nerve injury.

Macrophages and satellite glial cells are found between injured and uninjured neurons in the lumbar dorsal root ganglia (DRG). We explored the mechanism of neuro-immune and neuron-glia crosstalk leading to hyperexcitability of DRG neurons. After spared nerve injury (SNI), CX3CR1 resident macrophages became activated, proliferated, and increased inward-rectifying potassium channel K 2.

Characterisation of GFAP-Expressing Glial Cells in the Dorsal Root Ganglion after Spared Nerve Injury.

Satellite glial cells (SGCs), enveloping primary sensory neurons' somas in the dorsal root ganglion (DRG), contribute to neuropathic pain upon nerve injury. Glial fibrillary acidic protein (GFAP) serves as an SGC activation marker, though its DRG satellite cell specificity is debated. We employed the hGFAP-CFP transgenic mouse line, designed for astrocyte studies, to explore its expression within the peripheral nervous system (PNS) after spared nerve injury (SNI).

Microglial morphology in the somatosensory cortex across lifespan. A quantitative study.

Background: Microglia are long-lived cells that constantly monitor their microenvironment. To accomplish this task, they constantly change their morphology both in the short and long term under physiological conditions. This makes the process of quantifying physiological microglial morphology difficult.

The Antidiabetic Drug Metformin Regulates Voltage-Gated Sodium Channel Na1.7 via the Ubiquitin-Ligase NEDD4-2.

The antidiabetic drug metformin has been shown to reduce pain hypersensitivity in preclinical models of chronic pain and in neuropathic pain in humans. Multiple intracellular pathways have been described as metformin targets. Among them, metformin is an activator of the adenosine 5'-monophosphate protein kinase that can in turn modulate the activity of the E3 ubiquitin ligase NEDD4-2 and thus post-translational expression of voltage-gated sodium channels (Nas).

Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.

(1) Background: As membrane channels contribute to different cell functions, understanding the underlying mechanisms becomes extremely important. A large number of neuronal channels have been investigated, however, less studied are the channels expressed in the glia population, particularly in microglia. In the present study, we focused on the function of the Kv1.

The inhibition of Kir2.1 potassium channels depolarizes spinal microglial cells, reduces their proliferation, and attenuates neuropathic pain.

Spinal microglia change their phenotype and proliferate after nerve injury, contributing to neuropathic pain. For the first time, we have characterized the electrophysiological properties of microglia and the potential role of microglial potassium channels in the spared nerve injury (SNI) model of neuropathic pain. We observed a strong increase of inward currents restricted at 2 days after injury associated with hyperpolarization of the resting membrane potential (RMP) in microglial cells compared to later time-points and naive animals.

Recording of multiple ion current components and action potentials in human induced pluripotent stem cell-derived cardiomyocytes via automated patch-clamp.

Introduction: The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative proposes a three-step approach to evaluate proarrhythmogenic liability of drug candidates: effects on individual ion channels in heterologous expression systems, integrating these data into in-silico models of the electrical activity of human cardiomyocytes, and comparison with experiments on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Here we introduce patch-clamp electrophysiology techniques on hiPSC-CM to combine two of the CiPA steps in one assay.

Methods: We performed automated patch-clamp experiments on hiPSC-CM (Cor.

Intrathecal Administration of CXCL1 Enhances Potassium Currents in Microglial Cells.

The functioning of microglial cells inside the central nervous system depends on their ion channels expression. Microglia are capable of synthesizing different cytokines and chemokines, including CXCL1, and responding to their action via specific receptors. In this study, we explore the effect of intrathecal injection of CXCL1 on potassium currents, expressed in CX3CR1-Green Fluorescent Protein labeled microglia in transgenic mice.

CXCL1 activates TRPV1 via Gi/o protein and actin filaments.

Aims: CXCL1 is a chemokine with pleiotropic effects, including pain and itch. Itch, an unpleasant sensation that elicits the desire or reflex to scratch, it is evoked mainly from the skin and implicates activation of a specific subset of IB4+, C-type primary afferents. In previous studies we showed that acute application of CXCL1 induced a Ca influx of low amplitude and slow kinetics in a subpopulation of transient receptor potential vanilloid type 1 (TRPV1)+/isolectin B4 (IB4)+dorsal root ganglia neurons which also responded to other itch-inducing agents.