title: Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.
abstract: Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil. Electronic address: fernandahansen@hotmail.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Hansen
authors.affiliation: Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, 24020-141 Niterói, RJ, Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pandolfo
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Galland
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Felipe Vasconcelos
authors.initials: FV
authors.lastname: Torres
authors.affiliation: Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Trindade, 88040-970 Florianópolis, SC, Brazil.
authors.forename: Márcio Ferreira
authors.initials: MF
authors.lastname: Dutra
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Batassini
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Guerra
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Marina Concli
authors.initials: MC
authors.lastname: Leite
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D057967:Infusions, Intraventricular; D008124:Locomotion; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013997:Time Factors; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit; D018698:Glutamic Acid; D011765:Pyruvaldehyde; D020691:rab GTP-Binding Proteins; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione
keywords: Advanced glycation end products; Anxiety; Dementia; Diabetes; Glyoxalase 1; Methylglyoxal