GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

Abstract

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the vertebrate nervous system, serves as a signaling molecule modulating diverse processes during embryonic development. Earlier we have demonstrated that different forms of glutamic acid decarboxylase (GAD) are differentially regulated during mouse lens development. Here we show that the developing lens expresses also components of GABA signaling downstream of GAD. Multiple GABA A and GABA B receptor subunits as well as the GABA transporters show expression profiles highly correlated with the expression of different GADs. GABA receptors (GABAR) and the vesicular GABA transporter localize at the apical/basal membranes of the lens epithelia and differentiating fibers and may be involved in conventional GABAR-mediated signaling, while the membrane GABA transporters may also function as Na ؉ /Cl؊ /GABA carriers. The functionality of GABAR was verified by calcium imaging in whole lenses. Our data suggest that GABA synthesized locally by GAD, acts through GABA receptors by modulating the intracellular calcium levels. Developmental Dynamics 237:3830 -3841, 2008.

GluA2 AMPA glutamate receptor subunit exhibits codon 607 Q/R RNA editing in the lens

“…The present findings also appear consistent with Gamma-aminobutyric acid (GABA), GABA receptors and GABA-related enzymes expressed in the lens (27,28,30). GABA is the major inhibitory neurotransmitter and also linked with neural development and plasticity.…”

GABAAand GABABreceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+

“…We detected all but 2 ␣ subunits (namely ␣2 and ␣6), all ␥ subunits, as well as the ␦ and ε subunits, but only a single ␤ subunit (␤3). Expression of the ␥3 subunit is very restricted in the adult brain (6,7,53), but it is the most abundant ␥ subunit in mESCs, similar to the developing optic lens (37), pointing to the existence of common features of the embryonic GABA A R composition. The absence of ␤2 indicates mESCs lack the major "synaptic" GABA A R type composed of 2␣1/1␤2/2␥2 (5,6).…”

“…1A and Supplemental Table 1; ref. 37). We detected GABA A R ␣1, ␣3, ␣4, ␣5, ␤3, ␥1, ␥2S, ␥3, and ␦, as well as ε1 and ε2, but no ␣2, ␣6, ␤1, ␤2, or the GABA C R-specific 1 and 2 subunits in 1-d-old mESCs (Fig.…”

Sex- and age-related changes in GABA signaling components in the human cortex

“…These results suggest that the GAT3 upregulation in astrocytes might occur as a compensatory mechanism, but future studies using cell-type-specific markers have to be performed to test this hypothesis. Previous studies conducted in the developing mouse [119] and in perinatal hypoxia [15, 120], schizophrenia [121], and Alzheimer’s disease [9] reported similar compensatory mechanisms, and these are essential for the maintenance of GABA levels in the synapse.…”