Effect of Cannabidiol on the Synaptic Release of Glutamate from Neocortex of Patients with Drug-Resistant Epilepsy
Abstract number :
2.422
Submission category :
1. Basic Mechanisms / 1D. Mechanisms of Therapeutic Interventions
Year :
2023
Submission ID :
1266
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Christopher Martinez Aguirre, BS, MSc, PhD – Cinvestav
Cindy Santiago-Castañeda, BS, MSc, PhD – Pharmacobiology – Cinvestav; Francia Carmona-Cruz, BS – Pharmacobiology – Cinvestav; Mario Alonso-Vanegas, MD – International Center for Epilepsy Surgery – Hospital HMG-Coyoacán; Manola Cuéllar-Herrera, BS, MSc, PhD – Epilepsy Clinic – General Hospital of Mexico Dr. Eduardo Liceaga; Luisa Rocha, MD, MSc, PhD – Pharmacobiology – Cinvestav
Rationale:
Drug-resistant epilepsy (DRE) is associated with elevated extracellular levels of glutamate. Preclinical studies suggest that cannabidiol (CBD) decreases the brain release of glutamate. This study aims to evaluate the effect of CBD on the release of glutamate from cortical synaptic terminals of patients with DRE.
Methods:
Temporal (n=6) and extratemporal (n=10) neocortex from patients with DRE submitted to surgery were used. Synaptic terminals (synaptosomes) were obtained and incubated in vehicle or CBD (100 nM to 1 mM) for 15 minutes. They were subsequently exposed to KCl (30 mM) to evoke release of glutamate which was measured by HPLC. Basal glutamate release occurs without exposure to KCl.
Results:
Basal glutamate release was similar for both groups (temporal, 38.86 ± 5.36 nmol/mg protein; extratemporal 49.862 ± 4.44 nmol/mg protein). KCl (30 mM) increased glutamate release (temporal, 258%, p=0.0029; extratemporal, 193%, p=0.0002; vs baseline). The synaptosomes of the Temporal group exposed to CBD from 100 nM to 100 µM, presented lower glutamate values (-42% to -49%, p< 0.05 vs vehicle), effect not evident at 1 mM (-8%, p =0.9683 vs vehicle). The Extratemporal group showed similar changes with CBD from 100 nM to 10 µM (-52% to -55%, p< 0.05 vs vehicle), without being evident from 100 µM (-8% to -16% vs vehicle).
Basic Mechanisms