title: Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).
abstract: Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression.
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, PUCRS, Porto Alegre, RS, Brazil. Electronic address: katucapiotti@gmail.com.
authors.forename: Katiucia Marques
authors.initials: KM
authors.lastname: Capiotti
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, PUCRS, Porto Alegre, RS, Brazil. Electronic address: daiani.moraes@acad.pucrs.br.
authors.forename: Daiani Almeida
authors.initials: DA
authors.lastname: De Moraes
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, PUCRS, Porto Alegre, RS, Brazil. Electronic address: fabiano.menezes@acad.pucrs.br.
authors.forename: Fabiano Peres
authors.initials: FP
authors.lastname: Menezes
authors.affiliation: Laboratório de Biologia Genômica e Molecular, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, PUCRS, Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil. Electronic address: lwkist@gmail.com.
authors.forename: Luiza Wilges
authors.initials: LW
authors.lastname: Kist
authors.affiliation: Laboratório de Biologia Genômica e Molecular, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, PUCRS, Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil. Electronic address: mbogo@pucrs.br.
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, PUCRS, Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil. Electronic address: rosane.silva@pucrs.br.
authors.forename: Rosane Souza
authors.initials: RS
authors.lastname: Da Silva
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D005702:Galantamine / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D002800:Cholinesterase Inhibitors; D051274:Glucose Transporter Type 3; D005702:Galantamine; D011972:Receptor, Insulin; D000110:Acetylcholinesterase; D005947:Glucose
keywords: Cholinergic system; Diabetes mellitus; Glucose; Hyperglycemia; Locomotor activity; Memory