Electrophysiology of ionotropic GABA receptors

GABAA receptors are ligand-gated chloride channels and ionotropic receptors of GABA, the main inhibitory neurotransmitter in vertebrates. In this review, we discuss the major and diverse roles GABAA receptors play in the regulation of neuronal communication and the functioning of the brain. GABAA receptors have complex electrophysiological properties that enable them to mediate different types of currents such as phasic and tonic inhibitory currents. Their activity is finely regulated by membrane voltage, phosphorylation and several ions. GABAA receptors are pentameric and are assembled from a diverse set of subunits. They are subdivided into numerous subtypes, which differ widely in expression patterns, distribution and electrical activity. Substantial variations in macroscopic neural behavior can emerge from minor differences in structure and molecular activity between subtypes. Therefore, the diversity of GABAA receptors widens the neuronal repertoire of responses to external signals and contributes to shaping the electrical activity of neurons and other cell types.

Behavioural and neurochemical characterisation of the anxiolytic properties of an aqueous extract of Dysphania ambrosioides (L.) Mosyakin and Clemants (Chenopodiaceae) in experimental mice

Ethnopharmacological relevance: Dysphania ambrosioides (L.) Mosyakin & Clemants (Chenopodiaceae) is a medicinal plant known for its anxiolytic, antidepressant and anticonvulsant activities in Cameroonian folk medicine. Aim of the study: The aim of this work is to evaluate the anxiolytic effects of Dysphania ambrosioides aqueous extracts and investigate its mechanism of action. Materials and methods: Elevated plus maze test and open field test were used for detecting it anxiolytic properties. The possible mechanism of action of the aqueous extracts were investigated after pretreatment of animals with different antagonists of GABAA complex receptors (5 mg/kg N-methyl-β-carboline-3-carboxamide, 4 mg/kg flumazenil or 2 mg/kg bicuculline) 30 minutes prior to the oral administration of 370 mg/kg Dysphania ambrosioides aqueous extract. Results: Dysphania ambrosioides increased the percentage of entries into and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms, in the elevated plus maze. It reduced rearing and defecation, and increased crossing, in the open field. In addition, anxiolytic-like properties of Dysphania ambrosioides were blocked by different antagonists of GABAA complex receptors (N-methyl-β-carboline-3-carboxamide, flumazenil or bicuculline) as examined in elevated plus maze test. Finally, the activity of GABA-T activity was inhibited and the brain GABA concentration was increased by the extracts, respectively. Conclusion: These results suggest that Dysphania ambrosioides possess anxiolytic-like properties in mice that might involve an action on benzodiazepine and/or GABA sites in the GABAA receptor complex or by modulating brain GABA concentration in the central nervous system.

Magnetic Resonance Imaging (MRI) and Spectroscopy in Succinic Semialdehyde Dehydrogenase Deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of γ-aminobutyric acid (GABA) degradation, resulting in elevations of brain GABA and γ-hydroxybutyric acid (GHB). Previous magnetic resonance (MR) spectroscopy studies have shown increased levels of Glx in SSADH deficiency patients. Here in this work, we measure brain GABA in a large cohort of SSADH deficiency patients using advanced MR spectroscopy techniques that allow separation of GABA from overlapping metabolite peaks. We observed significant increases in GABA concentrations in SSADH deficiency patients for all 3 brain regions that were evaluated. Although GABA levels were higher in all 3 regions, each region had different patterns in terms of GABA changes with respect to age. We also report results from structural magnetic resonance imaging (MRI) of the same cohort compared with age-matched controls. We consistently observed signal hyperintensities in globus pallidus and cerebellar dentate nucleus.

Macromolecule suppressed GABA levels show no relationship with age in a pediatric sample

The inhibitory neurotransmitter γ-Aminobutyric acid (GABA) plays a crucial role in cortical development. Therefore, characterizing changes in GABA levels during development has important implications for the study of healthy development and developmental disorders. Brain GABA levels can be measured non-invasively using GABA-edited magnetic resonance spectroscopy (MRS). However, the most commonly used editing technique to measure GABA results in contamination of the GABA signal with macromolecules (MM). Therefore, GABA measured using this technique is often referred to as GABA+ . While few in number, previous studies have shown GABA+ levels increase with age during development. However, these studies are unable to specify whether it is specifically GABA that is increasing or, instead, if levels of MM increase. In this study, we use a GABA-editing technique specifically designed to suppress the MM signal (MM-supp GABA). We find no relationship between MM-supp GABA and age in healthy children aged 7–14 years. These findings suggest that the relationship between GABA+ and age is driven by changes in MM levels, not by changes in GABA levels. Moreover, these findings highlight the importance of accounting for MM levels in MRS quantification.