Martins 2017 Thesis

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Martins WC (2017) Estudo do efeito protetor da atorvastatina e dos eventos iniciais da neurotoxicidade induzida pelo peptídeo β-amilóide (Aβ1-40) em camundongos. Doctoral Thesis p85.

» Open Access

Martins WC (2017) Doctoral Thesis

Abstract: Alzheimer's disease (AD) is a neurological disorder that affects a large part of the world's population. It is characterized by memory loss, progressive dementia, behavioral changes and inability to perform routine activities. Histopathologically, AD presents the formation of plaques by the aggregation of amyloid-β peptides (Aβ) and neurofibrillary tangles, due to hyperphosphorylation of tau protein. The aim of this study was to investigate alterations in gene and protein expression related to AD and to evaluate the mechanisms involved in initial events of Aβ1-40 peptide toxicity after intracerebroventricular (i.c.v.) infusion. In addition, it was evaluated whether pre-treatment with atorvastatin prevents the toxic effects of this peptide. Adult male Swiss albino mice (3 months / 40-50g) were treated with atorvastatin 10 mg / kg / day, orally, or vehicle (0.9% saline) for 7 days. On the seventh day the aggregate form of Aβ1-40 (i.c.v., 400pmol / site) or saline was administered. After 24h, the animals were euthanized for biochemical analysis. The results show that atorvastatin is able to prevent the gene expression reduction of the postsynaptic protein PSD-95, the NMDA receptor GluN1 subunit and glutamatergic transporters GLAST and GLT-1 induced by Aβ1-40 infusion in the hippocampus. Aβ promoted a decrease in BDNF expression and an increase in reactive oxygen (ROS) and nitrogen (RNS) species levels. Pretreatment with atorvastatin was able to prevent the increased ROS and RNS. Through the evaluation of mitochondrial functionality by high resolution respirometry, we observed that Aβ1-40 did not significantly alter parameters of oxygen consumption. However, atorvastatin increased the mitochondrial respiratory capacity assessed in hippocampal homogenates. In conclusion, we observed that Aβ1-40 toxicity presents as initial events changes in proteins related to glutamatergic neurotransmission and oxidative stress. Atorvastatin prevents initial oxidative stress and increases mitochondrial respiratory capacity by an as yet unknown action mechanism, requiring further studies.

Keywords: Storvastatin, Amyloid-β peptide, Alzheimer’s disease, Glutamate transmission, Oxidative stress, Neuroprotection Bioblast editor: Kandolf G O2k-Network Lab: BR Florianapolis Latini A


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Alzheimer's 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS, ROX  HRR: Oxygraph-2k 

Labels, 2018-04