Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer's disease.
J Alzheimers Dis
; 33(4): 941-59, 2013.
Article
em En
| MEDLINE
| ID: mdl-23109558
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, accumulation of the amyloid-ß peptide (Aß), increase of oxidative stress, and synaptic alterations. The scavenging of reactive oxygen species through their matrix enzyme catalase is one of the most recognized functions of peroxisomes. The induction of peroxisome proliferation is attained through different mechanisms by a set of structurally diverse molecules called peroxisome proliferators. In the present work, a double transgenic mouse model of AD that co-expresses a mutant human amyloid-ß protein precursor (AßPPswe) and presenilin 1 without exon 9 (PS1dE9) was utilized in order to assess the effect of peroxisomal proliferation on Aß neurotoxicity in vivo. Mice were tested for spatial memory and their brains analyzed by cytochemical, electrophysiological, and biochemical methods. We report here that peroxisomal proliferation significantly reduces (i) memory impairment, found in this model of AD; (ii) Aß burden and plaque-associated acetylcholinesterase activity; (iii) neuroinflammation, measured by the extent of astrogliosis and microgliosis; and (iv) the decrease in postsynaptic proteins, while promoting synaptic plasticity in the form of long-term potentiation. We concluded that peroxisomal proliferation reduces various AD neuropathological markers and peroxisome proliferators may be considered as potential therapeutic agents against the disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Química Encefálica
/
Proliferadores de Peroxissomos
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Doença de Alzheimer
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Transtornos da Memória
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Degeneração Neural
Limite:
Animals
/
Humans
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Male
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Holanda