Front Neurosci. Jun 6; doi: /fnins eCollection Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the. Human and animal studies suggest an intriguing link between mitochondrial diseases and depression. Although depression has historically. Most of us have heard about the mitochondria in high school biology class. It's a part of all our cells (except red blood cells) and is considered.
Mood Mitochondria and
While attributing mood to a chemical has been long accepted, it may be a while before people accept the idea that changing mitochondrial movement statistics might better captures the effect.
Mitochondria source more than just ATP and calcium to various parts of the cell. As new probes like voltage and calcium imaging, and established techniques like Patch clamping are applied to mitochondria, a finer-grained picture of their correlations to the larger spiking activity of neurons may emerge.
The critical tool for observing mitochondria may ultimately be high resolution temperature imaging. Might mitochondria move along temperature gradients inside a neuron. If so, in what direction? Please sign in to add a comment. Registration is free, and takes less than a minute.
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Spinal cord is 'smarter' than previously thought 16 hours ago. What do you think about this particular story? Your message to the editors. Your email only if you want to be contacted back. E-mail the story Controlling mood through the motions of mitochondria. I would like to subscribe to Science X Newsletter. Note Your email address is used only to let the recipient know who sent the email. It would be of interest to map the dose-dependent effects of glucocorticoids on markers of mitochondrial function along with depression-like behavior to further confirm these relationships.
There has been quite a bit of work done to try to understand the effect of antidepressant drugs on mitochondrial function. Much of the research done to examine links between antidepressant drugs and mitochondrial function have used the SSRI fluoxetine, which may either inhibit or trigger mitochondrial apoptosis and alter activity of the ETC, depending on the cell type de Oliveira, The same effects were found in a later study on the rat brain, with fluoxetine decreasing the rate of ATP synthesis Curti et al.
These results indicate that high doses of fluoxetine have negative effects on mitochondria. Fluoxetine crosses mitochondrial membranes with ease, and it is possible that fluoxetine could interfere with membrane-bound proteins causing pro-apoptotic events de Oliveira, In vivo studies reveal a slightly more complex scenario, in that fluoxetine has both beneficial and detrimental effects on mitochondria when given systemically. Fluoxetine at the same dose also increased activity of ETC complex I in the hippocampus after one injection, but not in the prefrontal cortex or striatum Agostinho et al.
However, after 28 days of daily injections, complex IV activity was decreased in the hippocampus. These results suggest sex and region specific effects of systemic fluoxetine on mitochondrial function.
There has been some work done to examine the effect of other antidepressants. For example, chronic treatment with the tricyclic antidepressant imipramine as well as electroconvulsive shocks increased levels of cytochrome b mRNA in the rat cortex but not in the hippocampus, cerebellum or liver Huang et al. Finally, fluoxetine and desipramine enhanced cytochrome oxidase and glutamate dehydrogenase in presynaptic mitochondria located in the rat hippocampus Villa et al.
These data highlight the importance of antidepressants at a subcellular level and suggest that mitochondrial energy metabolism could be a mechanism of antidepressant drug action. Women are more than twice as likely to suffer from depression than men, but it is not yet clear why this occurs and whether or not it has a biological basis. There is evidence that gender differences might arise due to decreased levels of circulating estrogens Bloch et al.
Furthermore, administering estradiol alleviates depression-like symptoms in ovariectomized rats Rachman et al. The evidence linking mitochondria to estradiol and depression is sparse, but emerging. Some studies have indicated a protective role of estradiol in mitochondria, showing that it can inhibit the passage of ROS into mitochondria as well as preventing mitochondrial collapse and increasing the rate of ATP synthesis Wang et al.
Mitochondria are known to express estrogen and GRs in lung tissue, suggesting that mitochondria are responsive to fluctuating levels of stress hormones and estradiol Walf and Frye, It would be quite interesting to follow these studies with an investigation of brain mitochondria and estrogen receptors to determine whether sex steroid hormones in the brain might be involved in the gender differences seen in the prevalence of depression.
The specific biological mechanisms underlying major depression have yet to be elucidated. This review highlights the potential importance of mitochondrial function in depression. This is an area that has received relatively little experimental attention, but the data that have been published to date are promising and should be pursued.
Although one must be cautious in extrapolating findings from preclinical animal models to the human condition, there is evidence that chronic stress-induced inhibition of ETC complexes in the inner membrane of mitochondria is a contributing factor in the pathophysiology of depression. Dysfunctional mitochondria decrease the pool of available ATP, which could have detrimental effects on signal transduction pathways, dampening activity in neuronal circuits, and interfering with mitochondrial fusion and fission.
This negative cascade would ultimately increase oxidative stress, inflammatory responses, and pro-apoptotic events, some of which are known to be involved in the pathogenesis of depression. Viewed this way, it seems logical that reversing the early stages of mitochondrial dysfunction could provide a novel target for therapeutic intervention.
All authors contributed to the writing of this manuscript. JA wrote the first draft. JA constructed the figure. LK finalized the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. National Center for Biotechnology Information , U. Journal List Front Neurosci v. Published online Jun 6. Brymer , 2 Hector J. Caruncho , 1 and Lisa E.
Author information Article notes Copyright and License information Disclaimer. This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience. Received Feb 27; Accepted May The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
This article has been cited by other articles in PMC. Abstract Human and animal studies suggest an intriguing link between mitochondrial diseases and depression. Mitochondria Mitochondria are the main energy factories of eukaryotic cells. Open in a separate window. Genetics There have been many observations of links between mtDNA and depression.
Oxidative Stress Mitochondria are the primary source of ROS, which under normal conditions play important roles in cell signaling and homeostasis. Reelin, Oxidative Stress, Inflammation, and Depression A further link between ROS and depression has been suggested by recent work focused on the extracellular matrix protein reelin. Apoptosis Mitochondria have a clear role in cell metabolism, and evidence suggests that mitochondrial morphology also affects metabolic enzymes through fusion and fission Chen et al.
The Effect of Antidepressants on Mitochondria There has been quite a bit of work done to try to understand the effect of antidepressant drugs on mitochondrial function. Gender Differences in Depression and Mitochondria Women are more than twice as likely to suffer from depression than men, but it is not yet clear why this occurs and whether or not it has a biological basis. Conclusion The specific biological mechanisms underlying major depression have yet to be elucidated. Author Contributions All authors contributed to the writing of this manuscript.
Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Antidepressant action on mitochondrial dysfunction in psychiatric disorders. Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Olanzapine plus fluoxetine treatment alters mitochondrial respiratory chain activity in the rat brain.
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Mitochondrial Functions in Mood Disorders
The MHI outperformed individual mitochondrial function measures. Elevated positive mood at night was associated with higher MHI, and nightly. More than half of mitochondrial disease patients have comorbid mood disorders, and mice with neuron-specific accumulation of mtDNA. Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression. Frontiers in Neuroscience, ;.