Sexual ictal manifestations predominate in women with temporal lobe epilepsy: A finding suggesting sexual dimorphism in the human brain

Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET), [11C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A—binding potential (GABAA BPND) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABAA BPND were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu and ALFF, ReHo and GABAA BPND, and between ALFFs and GABAA BPND, controlling for rMRGlu. Brain-wide correlations between rMRGlu and ALFFs were significantly lower in TLE patients, and correlations between rMRGlu and GC were significantly greater in TLE than healthy subjects. These results indicate that the glutamatergic and GABAergic systems are coupled across the healthy human brain, and that ALFF is related to glutamate use throughout the healthy human brain. TLE may be a disorder of altered long-range connectivity in association with glutamate function.

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Temporal lobe epilepsy: a unique window into living human brain epigenetic gene regulation

Brain ◽

10.1093/brain/awu386 ◽

2015 ◽

Vol 138 (3) ◽

pp. 509-511 ◽

Cited By ~ 2

Author(s):

Alexander Grote ◽

Susanne Schoch ◽

Albert J. Becker

Keyword(s):

Gene Regulation ◽

Temporal Lobe Epilepsy ◽

Human Brain ◽

Temporal Lobe ◽

Epigenetic Gene Regulation

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Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2020.611278 ◽

2020 ◽

Vol 14 ◽

Author(s):

Christopher Martínez-Aguirre ◽

Francia Carmona-Cruz ◽

Ana Luisa Velasco ◽

Francisco Velasco ◽

Gustavo Aguado-Carrillo ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Human Brain ◽

Temporal Lobe ◽

Cell Membranes ◽

Epileptic Seizures ◽

Mesial Temporal Lobe Epilepsy ◽

Pharmacological Interaction ◽

Protein Activation ◽

High Concentrations ◽

Temporal Neocortex

Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT1A receptors. These receptors are coupled to Gi/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery (n = 11) and from a group of autopsies (n = 11). The [3H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT1A receptors. The [35S]-GTPγS assay was used to investigate the CBD-induced activation of Gi/o proteins through its action on 5-HT1A receptors.The CBD affinity (pKi) for 5-HT1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [35S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue (p > 0.05) at low CBD concentrations (1 pM to 10 μM). In contrast, at high concentrations (100 μM), CBD reduced the constitutive activity of Gi/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT1A receptors, in the autopsy group (hippocampus, 59.8%, p < 0.0001; temporal neocortex, 71.5%, p < 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p < 0.0001; temporal neocortex, 68.5%, p < 0.001). Our results show that CBD interacts with human 5-HT1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon Gi/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE.

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