Localization and expression of GABA transporters in the suprachiasmatic nucleus

Abstract

GABA is a principal neurotransmitter in the suprachiasmatic hypothalamic nucleus (SCN), the master circadian clock. Despite the importance of GABA and GABA uptake for functioning of the circadian pacemaker, the localization and expression of GABA transporters (GATs) in the SCN has not been investigated. The present studies used Western blot analysis, immunohistochemistry, and electron microscopy to demonstrate the presence of GABA transporter 1 (GAT1) and GABA transporter 3 (GAT3) in the SCN. By light microscopy, GAT1 and GAT3 were co-localized throughout the SCN, but were not expressed in the perikarya of arginine vasopressin- or vasoactive intestinal peptide-immunoreactive (−ir) neurons of adult rats, nor in the neuronal processes labeled with the Neurofilament Heavy Chain. By electron microscopy, GAT1- and GAT3-ir was found in glial processes surrounding unlabeled neuronal perikarya, axons, dendrites, and enveloped symmetric and asymmetric axo-dendritic synapses. Glial Fibrillary Acidic Protein-ir astrocytes grown in cell culture were immunopositive for GAT1 and GAT3 – and both GATs could be observed in the same glial cell. These data demonstrate that synapses in the SCN function as “tripartite” synapses consisting of presynaptic axon terminals, postsynaptic membranes, and astrocytes that contain GABA transporters. This model suggests that astrocytes expressing both GATs may regulate the extracellular GABA, and thereby modulate the activity of neuronal networks in the SCN.

Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms

“…The only neurotransmitter produced and received by all SCN neurons is g-aminobutyric acid (GABA) (Moore and Speh 1993;Moldavan et al 2015), which also modulates the phase relationships among SCN cells from day to day and across the seasons. Until recently, the role of GABA within the SCN was unclear.…”

The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus

“…Although all four types are found in the CNS, they are expressed differentially across brain regions and cell types (Gadea and Lopez-Colome, 2001; Moldavan et al, 2015). The most important transporters in the brain are GAT-1 and GAT-3 (Zhou and Danbolt, 2013; Zhou et al, 2012).…”

“…Interestingly, their distribution is not highly correlated with the distribution of glial fibrillary acidic protein (GFAP), an essential element within the cytoskeleton of astrocytes (Moldavan et al, 2015). GAT-1- and GAT-3-immunoreactivity has not been identified in SCN neurons but rather in a substantial number of SCN astrocytes (Fig.…”

“…It seems likely, however, that the role of GATs in determining the levels of extracellular GABA is far more extensive. GATs likely have a substantial role in determining the strength and mode of GABAergic neurotransmission in the SCN by both removing GABA from and releasing GABA into the extracellular space (Moldavan et al, 2015). …”

Dysmenorrhea: pathogenetic validation of pharmacotherapy

“…Глюкокортикоиды вызывают активацию перекисного окисления липидов и выход лизосомальных ферментов, в т. ч. фосфолипазы A2, и возрастает продукция ПГ. Кроме того, стрессорное воздействие повышает еще и продук-цию кортиколиберина и вазопрессина в паравентрику-лярном ядре (PVN) гипоталамуса, причем при усилении стрессора соотношение двух пептидов меняется в сторо-ну вазопрессина [10]. Важным патогенетическим звеном при стрессе являются повышенная тревожность, длитель-ная депрессия, связанные со снижением уровня ГАМК, который является важнейшим тормозным нейромедиато-ром центральной нервной системы человека.…”