PUBLICATION

Long-Term Methionine Exposure Induces Memory Impairment on Inhibitory Avoidance Task and Alters Acetylcholinesterase Activity and Expression in Zebrafish (Danio rerio)

Authors
Vuaden, F.C., Savio, L.E., Piato, A.L., Pereira, T.C., Vianna, M.R., Bogo, M.R., Bonan, C.D., and Wyse, A.T.
ID
ZDB-PUB-120327-2
Date
2012
Source
Neurochemical research   37(7): 1545-1553 (Journal)
Registered Authors
Bonan, Carla Denise, Vianna, Mônica Ryff Moreira Roca
Keywords
acetylcholinesterase, hypermethioninemia, memory, zebrafish
MeSH Terms
  • Acetylcholinesterase/metabolism*
  • Animals
  • Avoidance Learning*
  • Base Sequence
  • Brain/enzymology
  • DNA Primers
  • Memory Disorders/chemically induced*
  • Memory Disorders/enzymology
  • Methionine/administration & dosage*
  • Methionine/toxicity
  • Polymerase Chain Reaction
  • Zebrafish
PubMed
22437435 Full text @ Neurochem. Res.
Abstract

Hypermethioninemic patients exhibit a variable degree of neurological dysfunction. However, the mechanisms involved in these alterations have not been completely clarified. Cholinergic system has been implicated in many physiological processes, including cognitive performances, as learning, and memory. Parameters of cholinergic signaling have already been characterized in zebrafish brain. Since zebrafish is a small freshwater teleost which is a vertebrate model for modeling behavioral and functional parameters related to human pathogenesis and for clinical treatment screenings, in the present study we investigated the effects of short- and long-term methionine exposure on cognitive impairment, AChE activity and gene expression in zebrafish. For the studies, animals were exposed at two methionine concentrations (1.5 and 3.0 mM) during 1 h or 7 days (short- or long-term treatments, respectively). We observed a significant increase in AChE activity of zebrafish brain membranes after long-term methionine exposure at 3.0 mM. However, AChE gene expression decreased significantly in both concentrations tested after 7 days of treatment, suggesting that post-translational events are involved in the enhancement of AChE activity. Methionine treatment induces memory deficit in zebrafish after long-term exposure to this amino acid, which could be related, at least in part, with cognitive impairment observed in hypermethioninemia. Therefore, the results here presented raise a new perspective to use the zebrafish as a complementary vertebrate model for studying inborn errors of metabolism, which may help to better understand the pathophysiology of this disease.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping