A spatial threshold for astrocyte calcium surge.

Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which astrocyte calcium plays a crucial role. Synaptically evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e.

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging.

The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, and their role in stroke and aging. Melatonin has garnered significant attention in recent years due to its diverse physiological functions and potential therapeutic benefits by reducing oxidative stress, inflammation, and apoptosis. Melatonin has been found to mitigate ischemic brain damage caused by stroke.

A spatial threshold for astrocyte calcium surge.

Unlabelled: Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which the astrocyte calcium signal plays a crucial role. Synaptically-evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e.

Aluminum alters excitability by inhibiting calcium, sodium, and potassium currents in bovine chromaffin cells.

Aluminum (Al ) has long been related to neurotoxicity and neurological diseases. This study aims to describe the specific actions of this metal on cellular excitability and neurotransmitter release in primary culture of bovine chromaffin cells. Using voltage-clamp and current-clamp recordings with the whole-cell configuration of the patch clamp technique, online measurement of catecholamine release, and measurements of [Ca ] with Fluo-4-AM, we have observed that Al reduced intracellular calcium concentrations around 25% and decreased catecholamine secretion in a dose-dependent manner, with an IC of 89.

SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex.

Antisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential has generated hope for Alzheimer's disease (AD). We previously described that ablating SNCA encoding for α-synuclein (αSyn) in a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction of αSyn expression using ASO could be therapeutic in a mouse model of AD.

Spatial organization of neuron-astrocyte interactions in the somatosensory cortex.

Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons. Here, we show that Cannabinoid type 1 receptor (CB1R)-mediated astrocyte activation by neuron-released endocannabinoids elevate astrocyte Ca2+ levels, stimulate ATP/adenosine release as gliotransmitters, and transiently depress synaptic transmission in layer 5 pyramidal neurons at relatively distant synapses (˃20 μm) from the stimulated neuron.

Astrocyte-neuronal network interplay is disrupted in Alzheimer's disease mice.

Alzheimer's disease (AD) is associated with senile plaques of beta-amyloid (Aβ) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aβ on astroglial and neuronal network function remains unknown.

Dysregulation of Astrocyte-Neuronal Communication in Alzheimer's Disease.

Recent studies implicate astrocytes in Alzheimer's disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters.

Micromolar concentrations of Zn depress cellular excitability through a blockade of calcium current in rat adrenal slices.

The present work, using chromaffin cells in rat adrenal slices (RCCs), aims to describe what type of ionic current alterations induced by zinc underlies their effects reported on synaptic transmission. Thus, Zn blocked calcium channels of RCCs in a time- and concentration-dependent manner with an IC of 391 μM. This blockade was partially reversed upon washout and was greater at more depolarizing holding potentials (i.

Altered excitability and exocytosis in chromaffin cells from the R6/1 mouse model of Huntington's disease is linked to over-expression of mutated huntingtin.

As the peripheral sympathoadrenal axis is tightly controlled by the cortex via hypothalamus and brain stem, the central pathological features of Hunting's disease, (HD) that is, deposition of mutated huntingtin and synaptic dysfunctions, could also be expressed in adrenal chromaffin cells. To test this hypothesis we here present a thorough investigation on the pathological and functional changes undergone by chromaffin cells (CCs) from 2-month (2 m) to 7-month (7 m) aged wild-type (WT) and R6/1 mouse model of Huntington's disease (HD), stimulated with acetylcholine (ACh) or high [K ] (K ). In order to do this, we used different techniques such as inmunohistochemistry, patch-clamp, and amperometric recording.

Dual Antidepressant Duloxetine Blocks Nicotinic Receptor Currents, Calcium Signals and Exocytosis in Chromaffin Cells Stimulated with Acetylcholine.

The inhibition of nicotinic acetylcholine receptors (nAChRs) has been proposed as a potential strategy to develop new antidepressant drugs. This is based on the observation that antidepressants that selectively block noradrenaline (NA) or serotonin (5-HT) reuptake also inhibit nAChRs. Dual antidepressants blocking both NA and 5-HT reuptake were proposed to shorten the delay in exerting their clinical effects; whether duloxetine, a prototype of dual antidepressants, also blocks nAChRs is unknown.

Distinct patterns of exocytosis elicited by Ca, Sr and Ba in bovine chromaffin cells.

Three divalent cations can elicit secretory responses in most neuroendocrine cells, including chromaffin cells. The extent to which secretion is elicited by the cations in intact depolarized cells was Ba > Sr ≥ Ca, contrasting with that elicited by these cations in permeabilized cells (Ca > Sr > Ba). Current-clamp recordings show that extracellular Sr and Ba cause membrane depolarization and action potentials, which are not blocked by Cd but that can be mimicked by tetra-ethyl-ammonium.

Hydrogen sulphide facilitates exocytosis by regulating the handling of intracellular calcium by chromaffin cells.

Gasotransmitter hydrogen sulphide (HS) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of HS) and GYY4137 (GYY, slow donor of HS) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K-depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion.

L-type calcium channels in exocytosis and endocytosis of chromaffin cells.

The coexistence of different subtypes of voltage-dependent calcium channels (VDCC) within the same chromaffin cell (CC) and the marked interspecies variability in the proportion of VDCC subtypes that are present in the plasmalemma of the CCs raises the question on their roles in controlling different physiological functions. Particularly relevant seems to be the role of VDCCs in the regulation of the exocytotic neurotransmitter release process, and its tightly coupled membrane retrieval (endocytosis) process since both are Ca-dependent processes. This review is focused on the role of Ca influx through L-type VDCC in the regulation of these two processes.

Regulation by L channels of Ca(2+)-evoked secretory responses in ouabain-treated chromaffin cells.

It is known that the sustained depolarisation of adrenal medullary bovine chromaffin cells (BCCs) with high K(+) concentrations produces an initial sharp catecholamine release that subsequently fades off in spite depolarisation persists. Here, we have recreated a sustained depolarisation condition of BCCs by treating them with the Na(+)/K(+) ATPase blocker ouabain; in doing so, we searched experimental conditions that permitted the development of a sustained long-term catecholamine release response that could be relevant during prolonged stress. BCCs were perifused with nominal 0Ca(2+) solution, and secretion responses were elicited by intermittent application of short 2Ca(2+) pulses (Krebs-HEPES containing 2 mM Ca(2+)).

Chondroitin Sulfate Induces Depression of Synaptic Transmission and Modulation of Neuronal Plasticity in Rat Hippocampal Slices.

It is currently known that in CNS the extracellular matrix is involved in synaptic stabilization and limitation of synaptic plasticity. However, it has been reported that the treatment with chondroitinase following injury allows the formation of new synapses and increased plasticity and functional recovery. So, we hypothesize that some components of extracellular matrix may modulate synaptic transmission.

Different contributions of calcium channel subtypes to electrical excitability of chromaffin cells in rat adrenal slices.

We characterized the ionic currents underlying the cellular excitability and the Ca(2+) -channel subtypes involved in action potential (AP) firing of rat adrenal chromaffin cells (RCCs) preserved in their natural environment, the adrenal gland slices, through the perforated patch-clamp recording technique. RCCs prepared from adrenal slices exhibit a resting potential of -54 mV, firing spontaneous APs (2-3 spikes/s) generated by the opening of Na(+) and Ca(2+) -channels, and terminated by the activation of voltage and Ca(2+) -activated K(+) -channels (BK). Ca(2+) influx via L-type Ca(2+) -channels is involved in reaching threshold potential for AP firing, and is responsible for activation of BK-channels contributing to AP-repolarization and afterhyperpolarization, whereas P/Q-type Ca(2+) -channels are involved only in the repolarization phase.