De Paula Martins 2012 Thesis

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De Paula Martins R (2012) Altered mitochondrial ultrastructure, diminished content and energetics in the cerebral cortex from methylmercury-poisoned mice are prevented by diphenyl diselenide administration. Thesis Universidade Federal de Santa Catarina, Centro de Ciências Biológicas 104pp.

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De Paula Martins R (2012) Thesis Universidade Federal de Santa Catarina, Centro de Ciências Biológicas

Abstract: Considering that methylmercury (MeHg) exposure causes severe neurological damage in animals and humans, we have investigated the effects of MeHg poisoning on mitochondrial physiology in the brain and peripheral platelets of poisoned mice. Adult male mice exposed to MeHg (20 or 40mg/L) for twenty-one days showed a reduced ability for short-term object recognition. This MeHg-induced altered behavior, indicating discriminative short-memory impairment, was correlated with reduced NADH dehydrogenase, complex II and II-III activities in the cerebral cortex and with impaired systemic platelet oxygen consumption of intoxicated mice. Moreover, electron microscopy analysis showed enlarged and fused mitochondria leading to a reduced number of organelles in the MeHg-exposed cerebral cortex. Furthermore, cortical creatine kinase (CK) activity, a sensitive oxidative stress sensor, was almost abolished by the treatment. Next, MeHg-induced energetic impairment was studied in detail by evaluating the in vitro effect of MeHg exposure (0-1500 μM), in brain preparations. MeHg-exposed cortical slices evidenced the increase of hydrogen peroxide production, inhibition in MTT reduction and increased lactate formation. In addition, marked reduction of NADH dehydrogenase activity in cortical homogenates exposed to MeHg, during 15 or 60 minutes, was observed. Since the in vivo and in vitro MeHg-treatments induced mitochondrial dysfunction and oxidative stress, the effect from co-administration of diphenyl diselenide - (PhSe)2 – (subcutaneous administration; 5μmol/kg) was also investigated in MeHg-poisoned mice. (PhSe)2 treatment prevented from ultrastructural changes, mitochondrial content and the inhibitory effect on CK activity on MeHg-exposed mice. Therefore, these data strongly indicate MeHg poisoning probably compromises cell viability, by inducing mitochondrial oxidative stress, which could induce, in turn, to a mitochondrial fusion in order to conserve brain energy status. Additionally, we have also demonstrated that impaired systemic platelet oxygen consumption is a sensitive and non-invasive marker of the brain energy deficits induced by MeHg poisoning, and brain mitochondrial parameters could be prevented by (PhSe)2 co-administration.

Keywords: Methylmercury, Platelet mitochondrial respiration, Mitochondrial dysfunction, Diphenil diselenide

O2k-Network Lab: BR Florianapolis Latini A

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Mouse  Tissue;cell: Blood cells, Platelet  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET 

HRR: Oxygraph-2k