The action of neurotransmitters on the uptake of 45Ca2+ and the release of neuroactive amino acids from mammalian brain slices

1986 ◽  
Vol 14 (3) ◽  
pp. 625-626 ◽  
Author(s):  
JANET M. CROWDER ◽  
H. F. BRADFORD
Keyword(s):  
Amino Acids ◽  
Brain Slices ◽  
Mammalian Brain ◽  
Neuroactive Amino Acids

EFFECT OF IONS ON STIMULUS-INDUCED RELEASE OF AMINO ACIDS FROM MAMMALIAN BRAIN SLICES

1969 ◽  
Vol 16 (6) ◽  
pp. 961-967 ◽  
Author(s):  
R. I. Katz ◽  
T. N. Chase ◽  
I. J. Kopin
Keyword(s):  
Amino Acids ◽  
Brain Slices ◽  
Mammalian Brain

Atypical amino acids inhibit histidine, valine, or lysine transport into rat brain

1983 ◽  
Vol 245 (4) ◽  
pp. R556-R563 ◽  
Author(s):  
J. K. Tews ◽  
A. E. Harper
Keyword(s):  
Amino Acids ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
Brain Slices ◽  
Aromatic Amino Acids ◽  
Brain Barrier ◽  
Basic Amino Acids ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Single Meal

Transport of histidine, valine, or lysine into rat brain slices and across the blood-brain barrier (BBB) was determined in the presence of atypical nonprotein amino acids. Competitors of histidine and valine transport in slices were large neutral amino acids including norleucine, norvaline, alpha-aminooctanoate, beta-methylphenylalanine, and alpha-aminophenylacetate. Less effective were aromatic amino acids with ring substituents; ineffective were basic amino acids and omega-amino isomers of norleucine and aminooctanoate. Lysine transport was moderately depressed by homoarginine or ornithine plus arginine; large neutral amino acids were also similarly inhibitory. Histidine or valine transport across the BBB was also strongly inhibited by large neutral amino acids that were the most effective competitors in the slices (norvaline, norleucine, alpha-aminooctanoate, and alpha-aminophenylacetate); homoarginine and 8-aminooctanoate were ineffective. Homoarginine, ornithine, and arginine almost completely blocked lysine transport, but the large neutral amino acids were barely inhibitory. When rats were fed a single meal containing individual atypical large neutral amino acids or homoarginine, brain pools of certain large neutral amino acids or of arginine and lysine, respectively, were depleted.

Neuroactive amino acids in the area postrema

1992 ◽  
Vol 185 (6) ◽  
Author(s):  
Fred Walberg ◽  
OleP. Ottersen
Keyword(s):  
Amino Acids ◽  
Area Postrema ◽  
Neuroactive Amino Acids

Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy

Brain ◽  
2021 ◽  
Author(s):  
Dana Marafi ◽  
Jawid M Fatih ◽  
Rauan Kaiyrzhanov ◽  
Matteo P Ferla ◽  
Charul Gijavanekar ◽  
...  
Keyword(s):  
Amino Acids ◽  
Epileptic Encephalopathy ◽  
Molecular Diagnostic ◽  
Mammalian Brain ◽  
Global Developmental Delay ◽  
Metabolomic Analysis ◽  
Neutral Amino Acid Transporter ◽  
Family Based ◽  
Metabolic Biomarkers ◽  
Transmembrane Transporters

Abstract The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis.

Promiscuous enzymes generating d-amino acids in mammals: Why they may still surprise us?

2021 ◽  
Vol 478 (5) ◽  
pp. 1175-1178
Author(s):  
Herman Wolosker ◽  
Inna Radzishevsky
Keyword(s):  
Amino Acids ◽  
Mammalian Cells ◽  
Common Property ◽  
Mammalian Brain ◽  
Intercellular Signaling ◽  
Biochemical Pathway ◽  
Recent Issue ◽  
Threonine Dehydratase ◽  
Glutamate Synthesis ◽  
Potential Biomarkers

Promiscuous catalysis is a common property of enzymes, particularly those using pyridoxal 5′-phosphate as a cofactor. In a recent issue of this journal, Katane et al. Biochem. J. 477, 4221–4241 demonstrate the synthesis and accumulation of d-glutamate in mammalian cells by promiscuous catalysis mediated by a pyridoxal 5′-phosphate enzyme, the serine/threonine dehydratase-like (SDHL). The mechanism of SDHL resembles that of serine racemase, which synthesizes d-serine, a well-established signaling molecule in the mammalian brain. d-Glutamate is present in body fluids and is degraded by the d-glutamate cyclase at the mitochondria. This study demonstrates a biochemical pathway for d-glutamate synthesis in mammalian cells and advances our knowledge on this little-studied d-amino acid in mammals. d-Amino acids may still surprise us by their unique roles in biochemistry, intercellular signaling, and as potential biomarkers of disease.

scholarly journals Imaging Subthreshold Voltage Oscillation With Cellular Resolution in the Inferior Olive in vitro

2020 ◽  
Vol 14 ◽  
Author(s):  
Kevin Dorgans ◽  
Bernd Kuhn ◽  
Marylka Yoe Uusisaari
Keyword(s):  
Inferior Olive ◽  
Brain Slices ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Wide Field ◽  
Voltage Imaging ◽  
Subthreshold Oscillations ◽  
Cellular Resolution

Voltage imaging with cellular resolution in mammalian brain slices is still a challenging task. Here, we describe and validate a method for delivery of the voltage-sensitive dye ANNINE-6plus (A6+) into tissue for voltage imaging that results in higher signal-to-noise ratio (SNR) than conventional bath application methods. The not fully dissolved dye was injected into the inferior olive (IO) 0, 1, or 7 days prior to acute slice preparation using stereotactic surgery. We find that the voltage imaging improves after an extended incubation period in vivo in terms of labeled volume, homogeneous neuropil labeling with saliently labeled somata, and SNR. Preparing acute slices 7 days after the dye injection, the SNR is high enough to allow single-trial recording of IO subthreshold oscillations using wide-field (network-level) as well as high-magnification (single-cell level) voltage imaging with a CMOS camera. This method is easily adaptable to other brain regions where genetically-encoded voltage sensors are prohibitively difficult to use and where an ultrafast, pure electrochromic sensor, like A6+, is required. Due to the long-lasting staining demonstrated here, the method can be combined, for example, with deep-brain imaging using implantable GRIN lenses.

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