Glutamate derived γ-aminobutyric acid (GABA) is synthetized in the cytosol prior to delivery to the mitochondria where it is catabolized via the TCA cycle. GABA accumulates under various environmental conditions, but an increasing number of studies show its involvement at the crossroad between C and N metabolism. To assess the role of GABA in modulating cellular metabolism, we exposed seedlings of A. thaliana GABA transporter gat1 mutant to full nutrition medium and media deficient in C and N combined with feeding of different concentrations (0.5 and 1 mM) of exogenous GABA. GC-MS based metabolite profiling showed an expected effect of medium composition on the seedlings metabolism of mutant and wild type alike. That being said, a significant interaction between GAT1 deficiency and medium composition was determined with respect to magnitude of change in relative amino acid levels. The effect of exogenous GABA treatment on metabolism was contingent on both the medium and the genotype, leading for instance to a drop in asparagine under full nutrition and low C conditions and glucose under all tested media, but not to changes in GABA content. We additionally assessed the effect of GAT1 deficiency on the expression of glutamate metabolism related genes and genes involved in abiotic stress responses. These results suggest a role for GAT1 in GABA-mediated metabolic alterations in the context of the C-N equilibrium of plant cells.
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http://dx.doi.org/10.3389/fpls.2015.00785 | DOI Listing |
J Clin Invest
November 2024
Department of Pediatrics, UTSW Medical Center, Dallas, United States of America.
The SLC6A1 gene encodes the gamma-aminobutyric acid (GABA) transporter GAT-1, the deficiency of which is associated with infantile encephalopathy with intellectual disability. We designed two AAV9 vectors, with either the JeT or MeP promoter, and conducted preclinical gene therapy studies using heterozygous and homozygous Slc6a1 KO mice at different developmental ages and various routes of administration. Neonatal intracerebroventricular administration of either vector resulted in significantly normalized EEG patterns in Slc6a1-/- or Slc6a1+/- mice, as well as improvement in several behavioral phenotypes of Slc6a1-/- mice.
View Article and Find Full Text PDFHeliyon
November 2024
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
Inflammatory pain, an important form of common pain, negatively influences the quality of life. Pathway-selective optogenetic control is a popular tool in neuronal function research; however, attempts to modulate rodent behavior using pathway-selective optogenetics remain unverified. We developed a methodology for pathway-selective optogenetics in rats, focusing on the delivery of recombinant adeno-associated virus (rAAV) containing channelrhodopsin-2 (ChR2) injected at the "Zusanli" acupoints to the dorsal root ganglia (DRG) and toes, which is a part of the complex neuron network.
View Article and Find Full Text PDFDis Model Mech
November 2024
Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
ACS Chem Neurosci
November 2024
Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
Cell Rep Med
November 2024
Department of Clinic Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.
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