title: Platelet oxygen consumption as a peripheral blood marker of brain energetics in a mouse model of severe neurotoxicity.
abstract: Interactions of chemicals with cerebral cellular systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells, including platelets and/or peripheral blood lymphocytes. Therefore, here it was investigated whether peripheral blood markers may be useful for assessing the central toxic effects of methylmercury (MeHg). For this purpose, we investigated platelet mitochondrial physiology in a well-established mouse model of MeHg-induced neurotoxicity, and correlated this peripheral activity with behavioural and central biochemical parameters. In order to characterize the cortical toxicity induced by MeHg (20 and 40 mg/L in drinking water, 21 days), the behavioral parameter namely, short-term object recognition, and the central mitochondrial impairment assessed by measuring respiratory complexes I-IV enzyme activities were determined in MeHg-poisoned animals. Neurotoxicity induced by MeHg exposure provoked compromised cortical activity (memory impairment) and reduced NADH dehydrogenase, complex II and II-III activities in the cerebral cortex. These alterations correlated with impaired systemic platelet oxygen consumption of intoxicated mice, which was characterized by reduced electron transfer activity and uncoupled mitochondria. The data brought here demonstrated that impaired systemic platelet oxygen consumption is a sensitive and non-invasive marker of the brain energy deficits induced by MeHg poisoning. Finally, brain and platelets biochemical alterations significantly correlated with cognitive behavior in poisoned mice. Therefore, it could be proposed the use of platelet oxygen consumption as a peripheral blood marker of brain function in a mouse model MeHg-induced neurotoxicity.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil, robertamartinsss@gmail.com.
authors.forename: Roberta
authors.initials: R
authors.lastname: de Paula Martins
authors.forename: Viviane
authors.initials: V
authors.lastname: Glaser
authors.forename: Débora
authors.initials: D
authors.lastname: da Luz Scheffer
authors.forename: Priscila Maximiliana
authors.initials: PM
authors.lastname: de Paula Ferreira
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Paulo Alexandre
authors.initials: PA
authors.lastname: de Oliveira
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008767:Methylmercury Compounds; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000097:blood* / Q000378:metabolism; D009498:Neurotoxins; D010101:Oxygen Consumption / Q000502:physiology*; D011897:Random Allocation
chemical_list: D015415:Biomarkers; D008767:Methylmercury Compounds; D009498:Neurotoxins; C073972:dimethyl mercury