title: Long-term methionine exposure induces memory impairment on inhibitory avoidance task and alters acetylcholinesterase activity and expression in zebrafish (Danio rerio).
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.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil. fcvuaden@gmail.com
authors.forename: Fernanda Cenci
authors.initials: FC
authors.lastname: Vuaden
authors.forename: Luiz Eduardo B
authors.initials: LE
authors.lastname: Savio
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Piato
authors.forename: Talita C
authors.initials: TC
authors.lastname: Pereira
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Vianna
authors.forename: Maurício R
authors.initials: MR
authors.lastname: Bogo
authors.forename: Carla D
authors.initials: CD
authors.lastname: Bonan
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D017931:DNA Primers; D008569:Memory Disorders / Q000139:chemically induced* / Q000201:enzymology; D008715:Methionine / Q000008:administration & dosage* / Q000633:toxicity; D016133:Polymerase Chain Reaction; D015027:Zebrafish
chemical_list: D017931:DNA Primers; D008715:Methionine; D000110:Acetylcholinesterase