Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity

Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mit...
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Autor*in:	D’Acunzo, Pasquale [verfasserIn] Argyrousi, Elentina K. [verfasserIn] Ungania, Jonathan M. [verfasserIn] Kim, Yohan [verfasserIn] DeRosa, Steven [verfasserIn] Pawlik, Monika [verfasserIn] Goulbourne, Chris N. [verfasserIn] Arancio, Ottavio [verfasserIn] Levy, Efrat [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Alzheimer’s disease Down syndrome Extracellular vesicle Exosome Long-term potentiation MAO-B Microvesicle Mitochondria Mitovesicle Neurodegenerative disease

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Molecular neurodegeneration - BioMed Central, 2006, 19(2024), 1 vom: 14. Apr.
Übergeordnetes Werk:	volume:19 ; year:2024 ; number:1 ; day:14 ; month:04

Links:	Volltext

DOI / URN:	10.1186/s13024-024-00721-z

Katalog-ID:	SPR055523684

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520			\|a Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders.
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allfields	10.1186/s13024-024-00721-z doi (DE-627)SPR055523684 (SPR)s13024-024-00721-z-e DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid D’Acunzo, Pasquale verfasserin (orcid)0000-0001-7237-0076 aut Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. Alzheimer’s disease (dpeaa)DE-He213 Down syndrome (dpeaa)DE-He213 Extracellular vesicle (dpeaa)DE-He213 Exosome (dpeaa)DE-He213 Long-term potentiation (dpeaa)DE-He213 MAO-B (dpeaa)DE-He213 Microvesicle (dpeaa)DE-He213 Mitochondria (dpeaa)DE-He213 Mitovesicle (dpeaa)DE-He213 Neurodegenerative disease (dpeaa)DE-He213 Argyrousi, Elentina K. verfasserin (orcid)0000-0003-3716-807X aut Ungania, Jonathan M. verfasserin (orcid)0000-0003-3592-0846 aut Kim, Yohan verfasserin (orcid)0000-0003-2550-8751 aut DeRosa, Steven verfasserin aut Pawlik, Monika verfasserin (orcid)0000-0003-0138-7529 aut Goulbourne, Chris N. verfasserin (orcid)0000-0003-1185-2682 aut Arancio, Ottavio verfasserin (orcid)0000-0001-6335-164X aut Levy, Efrat verfasserin (orcid)0000-0001-6890-6763 aut Enthalten in Molecular neurodegeneration BioMed Central, 2006 19(2024), 1 vom: 14. Apr. (DE-627)515978361 (DE-600)2244557-2 1750-1326 nnns volume:19 year:2024 number:1 day:14 month:04 https://dx.doi.org/10.1186/s13024-024-00721-z X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-BIODIV SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 1 14 04
spelling	10.1186/s13024-024-00721-z doi (DE-627)SPR055523684 (SPR)s13024-024-00721-z-e DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid D’Acunzo, Pasquale verfasserin (orcid)0000-0001-7237-0076 aut Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. Alzheimer’s disease (dpeaa)DE-He213 Down syndrome (dpeaa)DE-He213 Extracellular vesicle (dpeaa)DE-He213 Exosome (dpeaa)DE-He213 Long-term potentiation (dpeaa)DE-He213 MAO-B (dpeaa)DE-He213 Microvesicle (dpeaa)DE-He213 Mitochondria (dpeaa)DE-He213 Mitovesicle (dpeaa)DE-He213 Neurodegenerative disease (dpeaa)DE-He213 Argyrousi, Elentina K. verfasserin (orcid)0000-0003-3716-807X aut Ungania, Jonathan M. verfasserin (orcid)0000-0003-3592-0846 aut Kim, Yohan verfasserin (orcid)0000-0003-2550-8751 aut DeRosa, Steven verfasserin aut Pawlik, Monika verfasserin (orcid)0000-0003-0138-7529 aut Goulbourne, Chris N. verfasserin (orcid)0000-0003-1185-2682 aut Arancio, Ottavio verfasserin (orcid)0000-0001-6335-164X aut Levy, Efrat verfasserin (orcid)0000-0001-6890-6763 aut Enthalten in Molecular neurodegeneration BioMed Central, 2006 19(2024), 1 vom: 14. Apr. (DE-627)515978361 (DE-600)2244557-2 1750-1326 nnns volume:19 year:2024 number:1 day:14 month:04 https://dx.doi.org/10.1186/s13024-024-00721-z X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-BIODIV SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 1 14 04
allfields_unstemmed	10.1186/s13024-024-00721-z doi (DE-627)SPR055523684 (SPR)s13024-024-00721-z-e DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid D’Acunzo, Pasquale verfasserin (orcid)0000-0001-7237-0076 aut Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. Alzheimer’s disease (dpeaa)DE-He213 Down syndrome (dpeaa)DE-He213 Extracellular vesicle (dpeaa)DE-He213 Exosome (dpeaa)DE-He213 Long-term potentiation (dpeaa)DE-He213 MAO-B (dpeaa)DE-He213 Microvesicle (dpeaa)DE-He213 Mitochondria (dpeaa)DE-He213 Mitovesicle (dpeaa)DE-He213 Neurodegenerative disease (dpeaa)DE-He213 Argyrousi, Elentina K. verfasserin (orcid)0000-0003-3716-807X aut Ungania, Jonathan M. verfasserin (orcid)0000-0003-3592-0846 aut Kim, Yohan verfasserin (orcid)0000-0003-2550-8751 aut DeRosa, Steven verfasserin aut Pawlik, Monika verfasserin (orcid)0000-0003-0138-7529 aut Goulbourne, Chris N. verfasserin (orcid)0000-0003-1185-2682 aut Arancio, Ottavio verfasserin (orcid)0000-0001-6335-164X aut Levy, Efrat verfasserin (orcid)0000-0001-6890-6763 aut Enthalten in Molecular neurodegeneration BioMed Central, 2006 19(2024), 1 vom: 14. Apr. (DE-627)515978361 (DE-600)2244557-2 1750-1326 nnns volume:19 year:2024 number:1 day:14 month:04 https://dx.doi.org/10.1186/s13024-024-00721-z X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-BIODIV SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 1 14 04
allfieldsGer	10.1186/s13024-024-00721-z doi (DE-627)SPR055523684 (SPR)s13024-024-00721-z-e DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid D’Acunzo, Pasquale verfasserin (orcid)0000-0001-7237-0076 aut Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. Alzheimer’s disease (dpeaa)DE-He213 Down syndrome (dpeaa)DE-He213 Extracellular vesicle (dpeaa)DE-He213 Exosome (dpeaa)DE-He213 Long-term potentiation (dpeaa)DE-He213 MAO-B (dpeaa)DE-He213 Microvesicle (dpeaa)DE-He213 Mitochondria (dpeaa)DE-He213 Mitovesicle (dpeaa)DE-He213 Neurodegenerative disease (dpeaa)DE-He213 Argyrousi, Elentina K. verfasserin (orcid)0000-0003-3716-807X aut Ungania, Jonathan M. verfasserin (orcid)0000-0003-3592-0846 aut Kim, Yohan verfasserin (orcid)0000-0003-2550-8751 aut DeRosa, Steven verfasserin aut Pawlik, Monika verfasserin (orcid)0000-0003-0138-7529 aut Goulbourne, Chris N. verfasserin (orcid)0000-0003-1185-2682 aut Arancio, Ottavio verfasserin (orcid)0000-0001-6335-164X aut Levy, Efrat verfasserin (orcid)0000-0001-6890-6763 aut Enthalten in Molecular neurodegeneration BioMed Central, 2006 19(2024), 1 vom: 14. Apr. (DE-627)515978361 (DE-600)2244557-2 1750-1326 nnns volume:19 year:2024 number:1 day:14 month:04 https://dx.doi.org/10.1186/s13024-024-00721-z X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-BIODIV SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 1 14 04
allfieldsSound	10.1186/s13024-024-00721-z doi (DE-627)SPR055523684 (SPR)s13024-024-00721-z-e DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid D’Acunzo, Pasquale verfasserin (orcid)0000-0001-7237-0076 aut Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. Alzheimer’s disease (dpeaa)DE-He213 Down syndrome (dpeaa)DE-He213 Extracellular vesicle (dpeaa)DE-He213 Exosome (dpeaa)DE-He213 Long-term potentiation (dpeaa)DE-He213 MAO-B (dpeaa)DE-He213 Microvesicle (dpeaa)DE-He213 Mitochondria (dpeaa)DE-He213 Mitovesicle (dpeaa)DE-He213 Neurodegenerative disease (dpeaa)DE-He213 Argyrousi, Elentina K. verfasserin (orcid)0000-0003-3716-807X aut Ungania, Jonathan M. verfasserin (orcid)0000-0003-3592-0846 aut Kim, Yohan verfasserin (orcid)0000-0003-2550-8751 aut DeRosa, Steven verfasserin aut Pawlik, Monika verfasserin (orcid)0000-0003-0138-7529 aut Goulbourne, Chris N. verfasserin (orcid)0000-0003-1185-2682 aut Arancio, Ottavio verfasserin (orcid)0000-0001-6335-164X aut Levy, Efrat verfasserin (orcid)0000-0001-6890-6763 aut Enthalten in Molecular neurodegeneration BioMed Central, 2006 19(2024), 1 vom: 14. Apr. (DE-627)515978361 (DE-600)2244557-2 1750-1326 nnns volume:19 year:2024 number:1 day:14 month:04 https://dx.doi.org/10.1186/s13024-024-00721-z X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-BIODIV SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 1 14 04
language	English
source	Enthalten in Molecular neurodegeneration 19(2024), 1 vom: 14. Apr. volume:19 year:2024 number:1 day:14 month:04
sourceStr	Enthalten in Molecular neurodegeneration 19(2024), 1 vom: 14. Apr. volume:19 year:2024 number:1 day:14 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Alzheimer’s disease Down syndrome Extracellular vesicle Exosome Long-term potentiation MAO-B Microvesicle Mitochondria Mitovesicle Neurodegenerative disease
dewey-raw	570
isfreeaccess_bool	true
container_title	Molecular neurodegeneration
authorswithroles_txt_mv	D’Acunzo, Pasquale @@aut@@ Argyrousi, Elentina K. @@aut@@ Ungania, Jonathan M. @@aut@@ Kim, Yohan @@aut@@ DeRosa, Steven @@aut@@ Pawlik, Monika @@aut@@ Goulbourne, Chris N. @@aut@@ Arancio, Ottavio @@aut@@ Levy, Efrat @@aut@@
publishDateDaySort_date	2024-04-14T00:00:00Z
hierarchy_top_id	515978361
dewey-sort	3570
id	SPR055523684
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR055523684</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240415064609.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240415s2024 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13024-024-00721-z</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR055523684</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13024-024-00721-z-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="q">DE-30</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">D’Acunzo, Pasquale</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-7237-0076</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2024</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. 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author	D’Acunzo, Pasquale
spellingShingle	D’Acunzo, Pasquale ddc 570 fid BIODIV misc Alzheimer’s disease misc Down syndrome misc Extracellular vesicle misc Exosome misc Long-term potentiation misc MAO-B misc Microvesicle misc Mitochondria misc Mitovesicle misc Neurodegenerative disease Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity
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topic_title	570 VZ BIODIV DE-30 fid Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity Alzheimer’s disease (dpeaa)DE-He213 Down syndrome (dpeaa)DE-He213 Extracellular vesicle (dpeaa)DE-He213 Exosome (dpeaa)DE-He213 Long-term potentiation (dpeaa)DE-He213 MAO-B (dpeaa)DE-He213 Microvesicle (dpeaa)DE-He213 Mitochondria (dpeaa)DE-He213 Mitovesicle (dpeaa)DE-He213 Neurodegenerative disease (dpeaa)DE-He213
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title	Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity
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title_full	Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity
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title_sort	mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity
title_auth	Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity
abstract	Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. © The Author(s) 2024
abstractGer	Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. © The Author(s) 2024
abstract_unstemmed	Background Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer’s disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders. © The Author(s) 2024
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title_short	Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity
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author2	Argyrousi, Elentina K. Ungania, Jonathan M. Kim, Yohan DeRosa, Steven Pawlik, Monika Goulbourne, Chris N. Arancio, Ottavio Levy, Efrat
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We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. Methods Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. Results Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. Conclusions Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Alzheimer’s disease</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Down syndrome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Extracellular vesicle</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Exosome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Long-term potentiation</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">MAO-B</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Microvesicle</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mitochondria</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mitovesicle</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neurodegenerative disease</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Argyrousi, Elentina K.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-3716-807X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ungania, Jonathan M.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-3592-0846</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Yohan</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-2550-8751</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">DeRosa, Steven</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pawlik, Monika</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-0138-7529</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Goulbourne, Chris N.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-1185-2682</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Arancio, Ottavio</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-6335-164X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Levy, Efrat</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-6890-6763</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Molecular neurodegeneration</subfield><subfield code="d">BioMed Central, 2006</subfield><subfield code="g">19(2024), 1 vom: 14. 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Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity

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