Functional Differences between Synaptic Mitochondria from the Striatum and the Cerebral Cortex

Maria Hvidberg Petersen; Cecilie Wennemoes Willert; Jens Velde Andersen; Helle Sønderby Waagepetersen; Niels Henning Skotte; Anne Nørremølle

doi:10.1016/j.neuroscience.2019.02.033

Functional Differences between Synaptic Mitochondria from the Striatum and the Cerebral Cortex

Maria Hvidberg Petersen, Cecilie Wennemoes Willert, Jens Velde Andersen, Helle Sønderby Waagepetersen, Niels Henning Skotte, Anne Nørremølle

2 Citationer (Scopus)

Abstract

Mitochondrial dysfunction has been shown to play a major role in neurodegenerative disorders such as Huntington's disease, Alzheimer's disease and Parkinson's disease. In these and other neurodegenerative disorders, disruption of synaptic connectivity and impaired neuronal signaling are among the early signs. When looking for potential causes of neurodegeneration, specific attention is drawn to the function of synaptic mitochondria, as the energy supply from mitochondria is crucial for normal synaptic function. Mitochondrial heterogeneity between synaptic and non-synaptic mitochondria has been described, but very little is known about possible differences between synaptic mitochondria from different brain regions. The striatum and the cerebral cortex are often affected in neurodegenerative disorders. In this study we therefore used isolated nerve terminals (synaptosomes) from female mice, striatum and cerebral cortex, to investigate differences in synaptic mitochondrial function between these two brain regions. We analyzed mitochondrial mass, citrate synthase activity, general metabolic activity and mitochondrial respiration in resting as well as veratridine-activated synaptosomes using glucose and/or pyruvate as substrate. We found higher mitochondrial oxygen consumption rate in both resting and activated cortical synaptosomes compared to striatal synaptosomes, especially when using pyruvate as a substrate. The higher oxygen consumption rate was not caused by differences in mitochondrial content, but instead corresponded with a higher proton leak in the cortical synaptic mitochondria compared to the striatal synaptic mitochondria. Our results show that the synaptic mitochondria of the striatum and cortex differently regulate respiration both in response to activation and variations in substrate conditions.

Originalsprog	Engelsk
Tidsskrift	Neuroscience
Vol/bind	406
Sider (fra-til)	432-443
Antal sider	12
ISSN	0306-4522
DOI	https://doi.org/10.1016/j.neuroscience.2019.02.033
Status	Udgivet - 15 maj 2019

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10.1016/j.neuroscience.2019.02.033

Citationsformater

@article{76075cbf577840c7ab14546236a522f1,

title = "Functional Differences between Synaptic Mitochondria from the Striatum and the Cerebral Cortex",

abstract = "Mitochondrial dysfunction has been shown to play a major role in neurodegenerative disorders such as Huntington's disease, Alzheimer's disease and Parkinson's disease. In these and other neurodegenerative disorders, disruption of synaptic connectivity and impaired neuronal signaling are among the early signs. When looking for potential causes of neurodegeneration, specific attention is drawn to the function of synaptic mitochondria, as the energy supply from mitochondria is crucial for normal synaptic function. Mitochondrial heterogeneity between synaptic and non-synaptic mitochondria has been described, but very little is known about possible differences between synaptic mitochondria from different brain regions. The striatum and the cerebral cortex are often affected in neurodegenerative disorders. In this study we therefore used isolated nerve terminals (synaptosomes) from female mice, striatum and cerebral cortex, to investigate differences in synaptic mitochondrial function between these two brain regions. We analyzed mitochondrial mass, citrate synthase activity, general metabolic activity and mitochondrial respiration in resting as well as veratridine-activated synaptosomes using glucose and/or pyruvate as substrate. We found higher mitochondrial oxygen consumption rate in both resting and activated cortical synaptosomes compared to striatal synaptosomes, especially when using pyruvate as a substrate. The higher oxygen consumption rate was not caused by differences in mitochondrial content, but instead corresponded with a higher proton leak in the cortical synaptic mitochondria compared to the striatal synaptic mitochondria. Our results show that the synaptic mitochondria of the striatum and cortex differently regulate respiration both in response to activation and variations in substrate conditions.",

author = "Petersen, {Maria Hvidberg} and Willert, {Cecilie Wennemoes} and Andersen, {Jens Velde} and Waagepetersen, {Helle S{\o}nderby} and Skotte, {Niels Henning} and Anne N{\o}rrem{\o}lle",

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TY - JOUR

T1 - Functional Differences between Synaptic Mitochondria from the Striatum and the Cerebral Cortex

AU - Petersen, Maria Hvidberg

AU - Willert, Cecilie Wennemoes

AU - Andersen, Jens Velde

AU - Waagepetersen, Helle Sønderby

AU - Skotte, Niels Henning

AU - Nørremølle, Anne

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Mitochondrial dysfunction has been shown to play a major role in neurodegenerative disorders such as Huntington's disease, Alzheimer's disease and Parkinson's disease. In these and other neurodegenerative disorders, disruption of synaptic connectivity and impaired neuronal signaling are among the early signs. When looking for potential causes of neurodegeneration, specific attention is drawn to the function of synaptic mitochondria, as the energy supply from mitochondria is crucial for normal synaptic function. Mitochondrial heterogeneity between synaptic and non-synaptic mitochondria has been described, but very little is known about possible differences between synaptic mitochondria from different brain regions. The striatum and the cerebral cortex are often affected in neurodegenerative disorders. In this study we therefore used isolated nerve terminals (synaptosomes) from female mice, striatum and cerebral cortex, to investigate differences in synaptic mitochondrial function between these two brain regions. We analyzed mitochondrial mass, citrate synthase activity, general metabolic activity and mitochondrial respiration in resting as well as veratridine-activated synaptosomes using glucose and/or pyruvate as substrate. We found higher mitochondrial oxygen consumption rate in both resting and activated cortical synaptosomes compared to striatal synaptosomes, especially when using pyruvate as a substrate. The higher oxygen consumption rate was not caused by differences in mitochondrial content, but instead corresponded with a higher proton leak in the cortical synaptic mitochondria compared to the striatal synaptic mitochondria. Our results show that the synaptic mitochondria of the striatum and cortex differently regulate respiration both in response to activation and variations in substrate conditions.

AB - Mitochondrial dysfunction has been shown to play a major role in neurodegenerative disorders such as Huntington's disease, Alzheimer's disease and Parkinson's disease. In these and other neurodegenerative disorders, disruption of synaptic connectivity and impaired neuronal signaling are among the early signs. When looking for potential causes of neurodegeneration, specific attention is drawn to the function of synaptic mitochondria, as the energy supply from mitochondria is crucial for normal synaptic function. Mitochondrial heterogeneity between synaptic and non-synaptic mitochondria has been described, but very little is known about possible differences between synaptic mitochondria from different brain regions. The striatum and the cerebral cortex are often affected in neurodegenerative disorders. In this study we therefore used isolated nerve terminals (synaptosomes) from female mice, striatum and cerebral cortex, to investigate differences in synaptic mitochondrial function between these two brain regions. We analyzed mitochondrial mass, citrate synthase activity, general metabolic activity and mitochondrial respiration in resting as well as veratridine-activated synaptosomes using glucose and/or pyruvate as substrate. We found higher mitochondrial oxygen consumption rate in both resting and activated cortical synaptosomes compared to striatal synaptosomes, especially when using pyruvate as a substrate. The higher oxygen consumption rate was not caused by differences in mitochondrial content, but instead corresponded with a higher proton leak in the cortical synaptic mitochondria compared to the striatal synaptic mitochondria. Our results show that the synaptic mitochondria of the striatum and cortex differently regulate respiration both in response to activation and variations in substrate conditions.

U2 - 10.1016/j.neuroscience.2019.02.033

DO - 10.1016/j.neuroscience.2019.02.033

M3 - Journal article

C2 - 30876983

SN - 0306-4522

VL - 406

SP - 432

EP - 443

JO - Neuroscience

JF - Neuroscience

ER -

Functional Differences between Synaptic Mitochondria from the Striatum and the Cerebral Cortex

Abstract

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