RESUMO
Synaptic aging has been associated with neuronal circuit dysfunction and cognitive decline. Reduced mitochondrial function may be an early event that compromises synaptic integrity and neurotransmission in vulnerable brain regions during physiological and pathological aging. Thus, we aimed to measure mitochondrial function in synapses from three brain regions at two different ages in the 3xTg-AD mouse model and in wild mice. We found that aging is the main factor associated with the decline in synaptic mitochondrial function, particularly in synapses isolated from the cerebellum. Accumulation of toxic compounds, such as tau and Aß, that occurred in the 3xTg-AD mouse model seemed to participate in the worsening of this decline in the hippocampus. The changes in synaptic bioenergetics were also associated with increased activation of the mitochondrial fission protein Drp1. These results suggest the presence of altered mechanisms of synaptic mitochondrial dynamics and their quality control during aging and in the 3xTg-AD mouse model; they also point to bioenergetic restoration as a useful therapeutic strategy to preserve synaptic function during aging and at the early stages of Alzheimer's disease (AD).
Assuntos
Envelhecimento/genética , Disfunção Cognitiva/genética , Dinaminas/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Envelhecimento/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Cerebelo/metabolismo , Cerebelo/fisiopatologia , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Dinaminas/metabolismo , Feminino , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Potencial da Membrana Mitocondrial/genética , Camundongos , Camundongos Transgênicos , Mitocôndrias/patologia , Neurônios/metabolismo , Neurônios/patologia , Especificidade de Órgãos , Sinapses/metabolismo , Sinapses/patologia , Sinaptossomos/metabolismo , Sinaptossomos/patologia , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
Mitochondrial activity is essential to support neural functions, and changes in the integrity and activity of the mitochondria can contribute to synaptic damage and neuronal death, especially in degenerative diseases associated with age, such as Alzheimer's and Parkinson's disease. Currently, different approaches are used to treat these conditions, and one strategy under research is mitochondrial transplantation. For years, mitochondria have been shown to be transferred between cells of different tissues. This process has allowed several attempts to develop transplantation schemes by isolating functional mitochondria and introducing them into damaged tissue in particular to counteract the harmful effects of myocardial ischemia. Recently, mitochondrial transfer between brain cells has also been reported, and thus, mitochondrial transplantation for disorders of the nervous system has begun to be investigated. In this review, we focus on the relevance of mitochondria in the nervous system, as well as some mitochondrial alterations that occur in neurodegenerative diseases associated with age. In addition, we describe studies that have performed mitochondrial transplantation in various tissues, and we emphasize the advances in mitochondrial transplantation aimed at treating diseases of the nervous system.