Redistribution of ASIC1a channels triggered by IL-6: Potential role of ASIC1a in neuroinflammation.

Cytokines, particularly IL-6, play a crucial role in modulating immune responses in the central nervous system (CNS). Elevated IL-6 levels have been observed in neuroinflammatory conditions, as well as in the sera and brains of patients with neurodegenerative diseases such as Parkinson's, Huntington's, Multiple Sclerosis, and Alzheimer's. Additionally, alterations in regional brain pH have been noted in these conditions.

Segmental Upregulation of ASIC1 Channels in the Formalin Acute Pain Mouse Model.

Background: Hindpaw injection of formalin in rodents is used to assess acute persistent pain. The response to formalin is biphasic. The initial response (first minutes) is thought to be linked to inflammatory, peripheral mechanisms, while the latter (around 30 min after the injection), is linked to central mechanisms.

Dynamic Distribution of ASIC1a Channels and Other Proteins within Cells Detected through Fractionation.

Proteins in eukaryotic cells reside in different cell compartments. Many studies require the specific localization of proteins and the detection of any dynamic changes in intracellular protein distribution. There are several methods available for this purpose that rely on the fractionation of the different cell compartments.

Signaling Pathways in Proton and Non-proton ASIC1a Activation.

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases as well as pain conditions. Classically, ASICs are described as transiently activated by a reduced pH, followed by desensitization; the activation allows sodium influx, and in the case of ASIC1a-composed channels, also calcium to some degree. Several factors are emerging and extensively analyzed as modulators, activating, inhibiting, and potentiating specific channel subunits.

Upregulation of ASIC1a channels in an in vitro model of Fabry disease.

Neuropathic pain is one of the key features of the classical phenotype of Fabry disease (FD). Acid sensing ion channels (ASICs) are H-gated cation channels, which belong to the epithelial sodium channel/DeGenerin superfamily, sensitive to the diuretic drug Amiloride. Molecular cloning has identified several distinct ASIC subunits.

Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction.

Acetazolamide (AZ), a molecule frequently used to treat different neurological syndromes, is an inhibitor of the carbonic anhydrase (CA), an enzyme that regulates pH inside and outside cells. We combined fluorescent FM styryl dyes and electrophysiological techniques at ex vivo levator auris longus neuromuscular junctions (NMJs) from mice to investigate the modulation of synaptic transmission and vesicle recycling by AZ. Transmitter release was minimally affected by AZ, as evidenced by evoked and spontaneous end-plate potential measurements.

Chronic pregabalin treatment decreases excitability of dentate gyrus and accelerates maturation of adult-born granule cells.

Pregabalin (PGB) is extensively prescribed to treat neurological and neuropsychiatrical conditions such as neuropathic pain, anxiety disorders, and epilepsy. Although PGB is known to bind selectively to the α2δ subunit of voltage-gated calcium channels, there is little understanding about how it exerts its therapeutic effects. In this article, we analyzed the effects of an in vivo chronic treatment with PGB over the physiology of dentate gyrus granule cells (DGGCs) using ex vivo electrophysiological and morphological analysis in adult mice.

Autoimmunity in amyotrophic lateral sclerosis: past and present.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting particularly motor neurons for which no cure or effective treatment is available. Although the cause of ALS remains unknown, accumulative evidence suggests an autoimmune mechanism of pathogenesis. In this paper, we will summarize the current research related to autoimmunity in the sporadic form of ALS and discuss the potential underlying pathogenic mechanisms and perspectives.