PUBLICATION

Methionine Exposure Alters Glutamate Uptake and Adenine Nucleotide Hydrolysis in the Zebrafish Brain

Authors
Vuaden, F.C., Savio, L.E., Rico, E.P., Mussulini, B.H., Rosemberg, D.B., de Oliveira, D.L., Bogo, M.R., Bonan, C.D., Wyse, A.T.
ID
ZDB-PUB-141126-2
Date
2016
Source
Molecular neurobiology   53(1): 200-9 (Journal)
Registered Authors
Bonan, Carla Denise
Keywords
Glutamate uptake, Inherited diseases, Hypermethioninemia, Methionine, Nucleotide catabolism, Zebrafish
MeSH Terms
  • Adenosine/metabolism
  • Adenosine Triphosphatases/metabolism
  • Adenosine Triphosphate/metabolism*
  • Amino Acid Metabolism, Inborn Errors/drug therapy
  • Animals
  • Brain/drug effects*
  • Brain/metabolism*
  • Glutamic Acid/metabolism*
  • Glycine N-Methyltransferase/deficiency
  • Hydrolysis/drug effects
  • Methionine/pharmacology*
  • Zebrafish
PubMed
25421208 Full text @ Mol. Neurobiol.
Abstract
Hypermethioninemic patients may exhibit different neurological dysfunctions, and the mechanisms underlying these pathologies remain obscure. Glutamate and ATP are important excitatory neurotransmitters co-released at synaptic clefts, and whose activities are intrinsically related. Adenosine-the final product of ATP breakdown-is also an important neuromodulator. Here, we investigated the effects of long-term (7-day) exposure to 1.5 or 3 mM methionine (Met) on glutamate uptake in brain tissues (telencephalon, optic tectum, and cerebellum) and on ATP, ADP, and AMP catabolism by ecto-nucleotidases found in brain membrane samples, using a zebrafish model. Also, we evaluated the expression of ecto-nucleotidase (ntdp1, ntdp2mg, ntdp2mq, ntdp2mv, ntdp3, and nt5e) and adenosine receptor (adora1, adora2aa, adora2ab, adora2b) genes in the brain of zebrafish exposed to Met. In animals exposed to 3.0 mM Met, glutamate uptake in the telencephalon decreased significantly. Also, ATP and ADP (but not AMP) catabolism decreased significantly at both Met concentrations tested. The messenger RNA (mRNA) levels of ntpd genes and of the adenosine receptors adora1 and adora2aa increased significantly after Met exposure. In contrast, adora2ab mRNA levels decreased after Met exposure. Our data suggest that glutamate and ATP accumulate at synaptic clefts after Met exposure, with potential detrimental effects to the nervous system. This phenomenon might explain, at least in part, the increased susceptibility of hypermethioninemic patients to neurological symptoms.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping