| 1. |
- Belenguer, Pascale, et al.
(författare)
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Mitochondria and the Brain : Bioenergetics and Beyond
- 2019
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Ingår i: Neurotoxicity Research. - : Springer Science and Business Media LLC. - 1029-8428 .- 1476-3524. ; 36:2, s. 219-238
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Tidskriftsartikel (refereegranskat)abstract
- The view of mitochondria acting solely as a powerhouse of the cell is no longer accurate. Besides cell bioenergetics, primary targets of mitochondrial studies include their interplay with essential processes within the cell, including redox and calcium homeostasis, and apoptosis. Recent studies evidence the dynamic behavior of mitochondria, continuously moving, fusing, and dividing, and the interaction of these events with cellular degeneration and plasticity in neural cells. Our review summarizes novel data and technologies that are developed and applied to the identification and clarification of the mitochondrial role in neural plasticity using both cultured cells and in vivo approaches. The complete understanding and modulation of such mechanisms may represent a novel and promising therapeutic approach for treatment of diseases affecting central and peripheral nervous system.
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| 2. |
- Richetin, Kevin, et al.
(författare)
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Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease
- 2017
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 102, s. 113-124
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Tidskriftsartikel (refereegranskat)abstract
- Adult hippocampal neurogenesis is strongly impaired in Alzheimer's disease (AD). In several mouse models of AD, it was shown that adult-born neurons exhibit reduced survival and altered synaptic integration due to a severe lack of dendritic spines. In the present work, using the APPxPS1 mouse model of AD, we reveal that this reduced number of spines is concomitant of a marked deficit in their neuronal mitochondrial content. Remarkably, we show that targeting the overexpression of the pro-neural transcription factor Neurod1 into APPxPS1 adult-born neurons restores not only their dendritic spine density, but also their mitochondrial content and the proportion of spines associated with mitochondria. Using primary neurons, a bona fide model of neuronal maturation, we identified that increases of mitochondrial respiration accompany the stimulating effect of Neurod1 overexpression on dendritic growth and spine formation. Reciprocally, pharmacologically impairing mitochondria prevented Neurod1-dependent trophic effects. Thus, since overexpression of Neurod1 into new neurons of APPxPS1 mice rescues spatial memory, our present data suggest that manipulating the mitochondrial system of adult-born hippocampal neurons provides neuronal plasticity to the AD brain. These findings open new avenues for far-reaching therapeutic implications towards neurodegenerative diseases associated with cognitive impairment.
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