AMPA receptor-mediated excitotoxicity has been implicated in the pathogenesis of stroke, neurotrauma, epilepsy, and many neurodegenerative diseases such as motoneuron disease. We studied the role of Cl- in AMPA receptor-mediated Ca2+-dependent excitotoxicity in cultured rat spinal motoneurons. Using the gramicidin perforated patch-clamp technique, the intracellular Cl- concentration could be calculated from the reversal potential of the GABA-induced current. The membrane depolarization caused by AMPA receptor stimulation resulted in Cl- influx through 5-nitro-2(3-phenylpropyl-amino) benzoic acid- and niflumic acid-sensitive Cl- channels. Cl- influx during AMPA receptor stimulation aggravated excitotoxic motoneuron death by two mechanisms: an increase of AMPA receptor conductance and an elevation of the Ca2+ driving force through a partial repolarization. The Cl- influx during AMPA receptor stimulation was enhanced by coadministration of GABA. This resulted in an increased Ca2+ influx and an enhanced cell death, suggesting that concomitant GABAergic stimulation may aggravate excitotoxic motoneuron death.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741175 | PMC |
| http://dx.doi.org/10.1523/JNEUROSCI.23-12-04942.2003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cognitive Outcomes After Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression: Résultats cognitifs après la stimulation magnétique transcrânienne pour le traitement de la dépression chez les personnes âgées.
Can J Psychiatry
January 2025
Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Background: Late-life depression (LLD) is often accompanied by cognitive impairment, which may persist despite antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) is an efficacious treatment for depression, with potential benefits on cognitive functioning. However, research on cognitive effects is inconclusive, relatively sparse in LLD, and predominantly focused on group-level cognitive changes.
View Article and Find Full Text PDFUnilateral whisker denervation activates plasticity mechanisms and circuit adaptations in adults. Single nucleus RNA sequencing and multiplex fluorescence in situ hybridization revealed differentially expressed genes related to altered glutamate receptor distributions and synaptogenesis in thalamocortical (TC) recipient layer 4 (L4) neurons of the sensory cortex, specifically those receiving input from the intact whiskers after whisker denervation. Electrophysiology detected increased spontaneous excitatory events at L4 neurons, confirming an increase in synaptic connections.
View Article and Find Full Text PDFEsketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.
Cell Biol Toxicol
January 2025
Laboratory of Neurobiology, Hebei Medical University, Shijiazhuang, 050017, China.
Esketamine, a newly developed antidepressant, is the subject of this research which seeks to explore its impact on depressive symptoms in neuropathic pain mice and the potential molecular mechanisms involved. Through transcriptome sequencing and bioinformatics analysis combined with in vivo studies, it was identified that esketamine markedly boosts the levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, allowing it to bind with GluA1 mRNA, promoting m6A modification, thereby enhancing GluA1 expression at synapses.
View Article and Find Full Text PDFSupraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex.
PLoS Biol
January 2025
Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, Fuzhou, China.
The anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC have been found, the specifics of the synaptic connections and the functional implications of the RSC-ACC projections remain less understood.
View Article and Find Full Text PDFA first morphological and electrophysiological characterization of Fañanas cells of the mouse cerebellum.
J Physiol
January 2025
Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France.
Fañanas cells (FCs) are cerebellar glia of unknown function. First described more than a century ago, they have been almost absent from the scientific literature ever since. Here, we combined whole-cell, patch clamp recordings, near-UV laser photolysis, dye-loading and confocal imaging for a first characterization of FCs in terms of their morphology, electrophysiology and glutamate-evoked currents.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!