Abstract
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.
Highlights
alcohol-exposed samples (Alcohol) use disorder (AUD) is ranked among the most prevalent mental disorders disproportionately affecting men (8.6% men vs. 1.7% women in 2016) (Rehm and Shield, 2019)
Our results suggest that chronic intermittent alcohol (CIA) impairs mitochondrial morphology and function in the medial prefrontal cortex (mPFC)
The three-dimensional serial block-face scanning electron microscopy (SBFSEM) study of mitochondria from mouse ACC showed elongated mitochondria in mice exposed to chronic alcohol
Summary
Alcohol use disorder (AUD) is ranked among the most prevalent mental disorders disproportionately affecting men (8.6% men vs. 1.7% women in 2016) (Rehm and Shield, 2019). Several brain regions, including the neocortex (especially frontal lobes), limbic system, and cerebellum, are known to be more vulnerable to the effects of alcohol (Moselhy et al, 2001; OscarBerman and Marinkovic, 2003; Sullivan, 2003). In line with these findings, PET, perfusion-weighted MRI, and SPECT showed a significant decrease in cortical metabolism (DaoCastellana et al, 1998; Gansler et al, 2000; Clark et al, 2007). According to our previous study, chronic intermittent alcohol (CIA) exposure triggers abnormal impulse and reward-seeking behaviors, which are associated with the mPFC and underlying changes in proteomic profiles (Starski et al, 2019a)
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