Abstract
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease that mimics many of the clinical and pathological features of multiple sclerosis. We have previously described a significant diminution in the GABAergic regulation of glutamate release from synaptosomes of EAE rats isolated during the acute stage of the disease. In order to explore the possible metabolic pathways responsible for this alteration, in this work we evaluate the direct effect of different GABAergic agonists on the glutamate release and concomitant synapsin I phosphorylation in synaptosomes from the frontal cortex of control and EAE animals. The results show that GABA as well as the GABA receptor agonists Muscimol (GABAA agonist) and Baclofen (GABAB agonist) caused a decrease in glutamate release in control rats paralleled by a similar reduction in synapsin I phosphorylation. Meanwhile synaptosomes from EAE animals are responsive only to Baclofen with respect to nontreated EAE synaptosomes, since glutamate release from the synaptosomes treated with Muscimol was similar to that observed in EAE rat synaptosomes which was already reduced as consequence of the disease. In the case of the benzodiazepines Diazepam and Clonazepam (GABAA allosteric agonists), both of them induced a reduction in glutamate release in synaptosomes from the CFA rats, effect that was only observed in synaptosomes of EAE rats treated with Clonazepam. In all cases both benzodiazepines showed a higher effect on synapsin I phosphorylation than in glutamate release. These results indicate that the extent of GABAergic modulation of presynaptic terminals depends on the type of agonist employed and this regulation is altered in the frontal cortex during the acute phase of EAE with respect to control animals.
Keywords: Autoimmunity, multiple sclerosis, synapsins, benzodiazepines, glutamate release, GABA
Graphical Abstract
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Drug Safety
Current Drug Targets
Current Medicinal Chemistry
Current Pharmaceutical Biotechnology
Central Nervous System Agents in Medicinal Chemistry
Letters in Drug Design & Discovery
Current Drug Discovery Technologies
Recent Advances in Anti-Infective Drug Discovery
Related Books
Computer-Aided Drug Discovery Methods: A Brief Introduction
Medicinal Plants, Phytomedicines and Traditional Herbal Remedies for Drug Discovery and Development against COVID-19
Frontiers in Drug Design and Discovery
Key Heterocyclic Cores for Smart Anticancer Drug–Design Part II
Key Heterocyclic Cores for Smart Anticancer Drug–Design Part I
Frontiers in Cardiovascular Drug Discovery
Frontiers in Drug Design and Discovery
Frontiers in Anti-Cancer Drug Discovery
Frontiers in Drug Design and Discovery
Anti-Obesity Drug Discovery and Development
32