Slc38a1 Conveys Astroglia-Derived Glutamine into GABAergic Interneurons for Neurotransmitter GABA Synthesis
CELLS
Authors: Qureshi, Tayyaba; Bjrkmo, Mona; Nordengen, Kaja; Gundersen, Vidar; Utheim, Tor Paaske; Watne, Leiv Otto; Storm-Mathisen, Jon; Hassel, Bjrnar; Chaudhry, Farrukh Abbas
Abstract
GABA signaling is involved in a wide range of neuronal functions, such as synchronization of action potential firing, synaptic plasticity and neuronal development. Sustained GABA signaling requires efficient mechanisms for the replenishment of the neurotransmitter pool of GABA. The prevailing theory is that exocytotically released GABA may be transported into perisynaptic astroglia and converted to glutamine, which is then shuttled back to the neurons for resynthesis of GABA-i.e., the glutamate/GABA-glutamine (GGG) cycle. However, an unequivocal demonstration of astroglia-to-nerve terminal transport of glutamine and the contribution of astroglia-derived glutamine to neurotransmitter GABA synthesis is lacking. By genetic inactivation of the amino acid transporter Solute carrier 38 member a1 (Slc38a1)-which is enriched on parvalbumin(+)GABAergic neurons-and by intraperitoneal injection of radiolabeled acetate (which is metabolized to glutamine in astroglial cells), we show that Slc38a1 mediates import of astroglia-derived glutamine into GABAergic neurons for synthesis of GABA. In brain slices, we demonstrate the role of Slc38a1 for the uptake of glutamine specifically into GABAergic nerve terminals for the synthesis of GABA depending on demand and glutamine supply. Thus, while leaving room for other pathways, our study demonstrates a key role of Slc38a1 for newly formed GABA, in harmony with the existence of a GGG cycle.
Characterization of aminoglycoside resistance genes and class 1 integrons in porcine and bovine gentamicin-resistant Escherichia coli
MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE
Authors: Sandvang, D; Aarestrup, FM
Abstract
A total of 78 gentamicin-resistant Escherichia coli strains from swine (27) and cattle (51) were characterized by phenotypic resistance, presence of selected aminoglycoside resistance genes, class 1 integrons and gene cassettes, and pulsed-field gel electrophoresis, Gentamicin resistance was mainly encoded by the ant(2")-I gene that was found in 76% of all the strains investigated, whereas the aac(3)-IIa gene was found in 14%, The ant(2")-I gene was predominant in strains from cattle, whereas the porcine strains contained both ant(2")-I, aac(3)-IIa, and the aac(3)-IVa genes. The pulsed-field gel electrophoresis (PFGE) investigation indicated a close clonal relationship in half of the bovine strains whereas the remaining E, coli were unrelated. Among the E, coli investigated, 20% contained class 1 integrons, Genes encoding resistance to trimethoprim (dhfrI, dhfrIb, and dhfrVII), gentamicin, tobramycin, and kanamycin (ant(2")-Ia streptomycin and spectinomycin (ant(3")-Ia) and streptothricin (sat1) were identified as gene cassettes. The most prevalent gene cassettes were ant(3")-Ia (11 isolates) and the dhfrI (nine isolates).