Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice
Alcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual’s life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cogniti...
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doaj-414f555b714042c7b39dc272b9ebe44a2020-11-25T03:42:20ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-10-011410.3389/fnins.2020.561173561173Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of MicePei Shang0Pei Shang1Daniel Lindberg2Phillip Starski3Lee Peyton4Sa-Ik Hong5Sun Choi6Doo-Sup Choi7Doo-Sup Choi8Doo-Sup Choi9Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesDepartment of Neurology, First Hospital of Jilin University, Changchun, ChinaDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesNeuroscience Program, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesNeuroscience Program, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic College of Medicine and Science, Rochester, MN, United StatesAlcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual’s life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cognitive and executive dysfunction. The mPFC contains more mitochondria compared to other cortical areas, which suggests mitochondrial damage may occur in AUD and trigger subsequent behavior change. Here, we identified morphological and functional changes in mitochondria in the mPFC in C57BL6/J mice after 8 h of withdrawal from chronic intermittent alcohol (CIA) exposure. Three-dimensional serial block-face scanning electron microscopy (SBFSEM) reconstruction revealed that CIA exposure elongated mPFC mitochondria and formed mitochondria-on-a-string (MOAS). Furthermore, alcohol significantly affected mitochondrial bioenergetics, including oxidative phosphorylation and electron transport, with inhibited aerobic respiration in mPFC mitochondria after CIA exposure. We also found decreased expression of fusion (mitofusin 2, Mfn2) and increased fission (mitochondrial fission 1 protein, Fis1) proteins in the mPFC of alcohol-treated mice. In sum, our study suggests that CIA exposure impairs mitochondrial dynamics and function in the mPFC.https://www.frontiersin.org/articles/10.3389/fnins.2020.561173/fullalcohol use disorderfissionfusionmedial prefrontal cortexmitochondriamorphology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pei Shang Pei Shang Daniel Lindberg Phillip Starski Lee Peyton Sa-Ik Hong Sun Choi Doo-Sup Choi Doo-Sup Choi Doo-Sup Choi |
spellingShingle |
Pei Shang Pei Shang Daniel Lindberg Phillip Starski Lee Peyton Sa-Ik Hong Sun Choi Doo-Sup Choi Doo-Sup Choi Doo-Sup Choi Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice Frontiers in Neuroscience alcohol use disorder fission fusion medial prefrontal cortex mitochondria morphology |
author_facet |
Pei Shang Pei Shang Daniel Lindberg Phillip Starski Lee Peyton Sa-Ik Hong Sun Choi Doo-Sup Choi Doo-Sup Choi Doo-Sup Choi |
author_sort |
Pei Shang |
title |
Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice |
title_short |
Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice |
title_full |
Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice |
title_fullStr |
Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice |
title_full_unstemmed |
Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice |
title_sort |
chronic alcohol exposure induces aberrant mitochondrial morphology and inhibits respiratory capacity in the medial prefrontal cortex of mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2020-10-01 |
description |
Alcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual’s life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cognitive and executive dysfunction. The mPFC contains more mitochondria compared to other cortical areas, which suggests mitochondrial damage may occur in AUD and trigger subsequent behavior change. Here, we identified morphological and functional changes in mitochondria in the mPFC in C57BL6/J mice after 8 h of withdrawal from chronic intermittent alcohol (CIA) exposure. Three-dimensional serial block-face scanning electron microscopy (SBFSEM) reconstruction revealed that CIA exposure elongated mPFC mitochondria and formed mitochondria-on-a-string (MOAS). Furthermore, alcohol significantly affected mitochondrial bioenergetics, including oxidative phosphorylation and electron transport, with inhibited aerobic respiration in mPFC mitochondria after CIA exposure. We also found decreased expression of fusion (mitofusin 2, Mfn2) and increased fission (mitochondrial fission 1 protein, Fis1) proteins in the mPFC of alcohol-treated mice. In sum, our study suggests that CIA exposure impairs mitochondrial dynamics and function in the mPFC. |
topic |
alcohol use disorder fission fusion medial prefrontal cortex mitochondria morphology |
url |
https://www.frontiersin.org/articles/10.3389/fnins.2020.561173/full |
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