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1.
Mol Neurobiol ; 49(1): 222-33, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23893294

RESUMO

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.


Assuntos
Canabidiol/farmacologia , Caspase 3/biossíntese , Dinaminas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Sobrecarga de Ferro/metabolismo , Dinâmica Mitocondrial/fisiologia , Fármacos Neuroprotetores/farmacologia , Sinaptofisina/biossíntese , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Canabidiol/uso terapêutico , Feminino , Sobrecarga de Ferro/prevenção & controle , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Gravidez , Distribuição Aleatória , Ratos , Ratos Wistar
2.
Mol Neurobiol ; 46(2): 467-74, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22810802

RESUMO

In the present study, we investigated whether sepsis induced by cecal ligation and puncture (CLP) modifies Na(+), K(+)-ATPase activity, mRNA expression, and cerebral edema in hippocampus and cerebral cortex of rats and if antioxidant (ATX) treatment prevented the alterations induced by sepsis. Rats were subjected to CLP and were divided into three groups: sham; CLP-rats were subjected to CLP without any further treatment; and ATX-CLP plus administration of N-acetylcysteine plus deferoxamine. Several times (6, 12, and 24) after CLP or sham operation, the rats were killed and hippocampus and cerebral cortex were isolated. Na(+), K(+)-ATPase activity was inhibited in the hippocampus 24 h after sepsis, and ATX treatment was not able to prevent this inhibition. The Na(+), K(+)-ATPase activity also was inhibited in cerebral cortex 6, 12, and 24 h after sepsis. No differences on Na(+), K(+)-ATPase catalytic subunit mRNA levels were found in the hippocampus and cerebral cortex after sepsis. ATX treatment prevents Na(+), K(+)-ATPase inhibition only in the cerebral cortex. Na(+), K(+)-ATPase inhibition was not associated to increase brain water content. In conclusion, the present study demonstrated that sepsis induced by CLP inhibits Na(+), K(+)-ATPase activity in a mechanism dependent on oxidative stress, but this is not associated to increase brain water content.


Assuntos
Antioxidantes/farmacologia , Córtex Cerebral/enzimologia , Hipocampo/enzimologia , Sepse/enzimologia , Sepse/patologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Domínio Catalítico , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sepse/genética , ATPase Trocadora de Sódio-Potássio/genética , Água/metabolismo
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