Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease
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 m...
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doaj-75699b6163c44ace81cc7a0fb09b1a4e2021-03-22T12:45:15ZengElsevierNeurobiology of Disease1095-953X2017-06-01102113124Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's diseaseKevin Richetin0Manon Moulis1Aurélie Millet2Macarena S. Arràzola3Trinovita Andraini4Jennifer Hua5Noélie Davezac6Laurent Roybon7Pascale Belenguer8Marie-Christine Miquel9Claire Rampon10Centre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, France; Department of Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceStem Cell Laboratory for CNS Diseases Modeling, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund Stem Cell Center and MultiPark, Lund University, BMC A10, 221 84 Lund, SwedenCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, FranceCentre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, France; Corresponding author at: UMR5169 CNRS, Centre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse Cedex 9, France.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.http://www.sciencedirect.com/science/article/pii/S0969996117300517Adult neurogenesisNeurod1MitochondriaDentate gyrusAlzheimer's disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kevin Richetin Manon Moulis Aurélie Millet Macarena S. Arràzola Trinovita Andraini Jennifer Hua Noélie Davezac Laurent Roybon Pascale Belenguer Marie-Christine Miquel Claire Rampon |
spellingShingle |
Kevin Richetin Manon Moulis Aurélie Millet Macarena S. Arràzola Trinovita Andraini Jennifer Hua Noélie Davezac Laurent Roybon Pascale Belenguer Marie-Christine Miquel Claire Rampon Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease Neurobiology of Disease Adult neurogenesis Neurod1 Mitochondria Dentate gyrus Alzheimer's disease |
author_facet |
Kevin Richetin Manon Moulis Aurélie Millet Macarena S. Arràzola Trinovita Andraini Jennifer Hua Noélie Davezac Laurent Roybon Pascale Belenguer Marie-Christine Miquel Claire Rampon |
author_sort |
Kevin Richetin |
title |
Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease |
title_short |
Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease |
title_full |
Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease |
title_fullStr |
Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease |
title_full_unstemmed |
Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease |
title_sort |
amplifying mitochondrial function rescues adult neurogenesis in a mouse model of alzheimer's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2017-06-01 |
description |
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. |
topic |
Adult neurogenesis Neurod1 Mitochondria Dentate gyrus Alzheimer's disease |
url |
http://www.sciencedirect.com/science/article/pii/S0969996117300517 |
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