PUBLICATION

Inhibitory effect of lithium on nucleotide hydrolysis and acetylcholinesterase activity in zebrafish (Danio rerio) brain

Authors
Oliveira, R.D., Seibt, K.J., Rico, E.P., Bogo, M.R., and Bonan, C.D.
ID
ZDB-PUB-110603-12
Date
2011
Source
Neurotoxicology and teratology   33(6): 651-7 (Journal)
Registered Authors
Bonan, Carla Denise
Keywords
acetylcholinsterase, ectonucleotidases, lithium chloride, zebrafish, nucleoside triphosphate diphosphohydrolases, ecto-5'-nucleotidase
MeSH Terms
  • Acetylcholinesterase/genetics
  • Acetylcholinesterase/metabolism*
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism
  • Animals
  • Brain/drug effects*
  • Brain/enzymology
  • Brain/metabolism
  • Cholinesterase Inhibitors/pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression/drug effects
  • Hydrolysis
  • Lithium/pharmacology*
  • Male
  • Nucleotides/genetics
  • Nucleotides/metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish/metabolism*
PubMed
21609761 Full text @ Neurotoxicol. Teratol.
Abstract
Lithium has been used as an effective antimanic drug in humans and it is well known for its effects on neuropsychiatric disorders and neuronal communication. ATP and adenosine are important signaling molecules, and most nerves release ATP as a fast co-transmitter together with classical neurotransmitters such as acetylcholine. In this study, we evaluated the in vitro and in vivo effects of lithium on acetylcholinesterase and ectonucleotidase activities in zebrafish brain. There was a significant inhibition of ADP hydrolysis after in vivo exposure to lithium at 5 and 10mg/l (27.6% and 29% inhibition, respectively), whereas an inhibitory effect was observed for AMP hydrolysis only at 10mg/l (30%). Lithium treatment in vivo also significantly decreased the acetylcholinesterase activity at 10mg/l (21.9%). The mRNA transcript levels of the genes encoding for these enzymes were unchanged after exposure to 5 and 10mg/l lithium chloride. In order to directly evaluate the action of lithium on enzyme activities, we tested the in vitro effect of lithium at concentrations ranging from 1 to 1000µM. There were no significant changes in zebrafish brain ectonucleotidase and acetylcholinesterase activities at all concentrations tested in vitro. Our findings show that lithium treatment can alter ectonucleotidase and acetylcholinesterase activities, which may regulate extracellular nucleotide, nucleoside, and acetylcholine levels. These data suggest that cholinergic and purinergic signaling may be targets of the pharmacological effects induced by this compound.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping