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.
and Mood Mitochondria
As a result of the their roles in energy production, mitochondria also generate reactive oxygen species ROS that may have a toxic effects in cells. In addition, mitochondria also play a prominent role in the regulation of apoptotic cell death for examples, see Davidson and Hardison, ; Herrmann and Neupert, ; Calabrese et al. The focus of this review is the link between mitochondrial dysfunction and major depression. Depression has historically been considered a disorder of altered pharmacology and altered hippocampal neurogenesis.
However, recent evidence has opened the door to an expanded notion of the neurobiology of depression, such that a reduction in ATP levels, enhancement of oxidative stress, and acceleration of apoptosis are now considered to be important events reviewed in Rezin et al. Uncovering how all these factors influence one another could lead to new vistas in the development of novel therapeutics for the treatment of this problematic disorder.
The mitochondrion under normal physiological conditions and in the depression brain. As detailed in the right side of the image, there are a series of mitochondrial alterations that have been observed both in depressed patients and in animal models of depression red lines.
These include changes affecting mitochondrial DNA, membrane permeability, and increased formation of reactive oxygen species ROS. As a consequence, these alterations lead to pro-inflammatory activity, increased apoptosis, and dampened synaptic plasticity and neuronal differentiation. See the text for more detailed explanations. The presence and severity of symptoms vary among individuals, and can include low mood and anhedonia, decreased energy, altered appetite and weight, irritability, sleep disturbances, and cognitive deficits Nemeroff, Patients with depression have a higher rate of other physical illnesses i.
The complexity of this disorder is further compounded by the fact that it often co-occurs with other psychiatric conditions. It is generally thought that a combination of environmental and genetic factors influences the development of depression Nestler et al. However, despite extensive clinical and preclinical research efforts, there is still a fundamental lack of understanding about the specific biological changes that give rise to depressive symptoms.
For more than 50 years, the dominant theory for the pathogenesis of depression was the monoamine hypothesis Schildkraut, , which arose from observations that antidepressant drugs work by inhibiting the reuptake of monoamines such as serotonin and norepinephrine. More recent theories about the neurobiological basis of depression have focused on the neurogenesis theory, which posits that stress-induced decreases in hippocampal neurogenesis could be a causal factor in depression Jacobs et al.
This hypothesis is supported by observations of decreased hippocampal volume in patients with depression MacQueen et al. Our laboratory has contributed to this literature using a well-validated preclinical model of depression in which rats or mice are subjected to daily injections of the stress hormone corticosterone CORT for several weeks, followed by behavioral testing and then tissue collection for further analyses Gregus et al.
Using this approach, we showed that the time course for the onset of depression-like behavior in rats is paralleled by dampened hippocampal neurogenesis and neuronal maturation Lussier et al. Importantly, this work also implicated the extracellular matrix protein reelin in the pathogenesis of depression see Caruncho et al.
There is evidence that reelin can regulate adult hippocampal neurogenesis and dendritic spine plasticity Pujadas et al. The reelin link is relevant to mitochondrial dysfunction because reelin in the periphery interacts with the immune system and a loss of reelin can magnify markers of inflammation that influence mitochondria Green-Johnson et al.
This issue is discussed in more detail in the section below on reelin and inflammation. It is important to note that the neurogenesis hypothesis of depression is somewhat controversial because depression-like symptoms can occur even when cell proliferation is not decreased and the behavioral actions of antidepressants do not always coincide with increases in the number of hippocampal neurons Surget et al.
Instead, some data suggest that depression and the therapeutic actions of antidepressants may be more related to alterations in dendritic complexity and neuronal remodeling than cell number per se Bessa et al. The neurogenesis hypothesis of depression may therefore be better described as the neuroplasticity hypothesis of depression — a broadening of concept that would include plasticity within the cell, such as mitochondrial activity.
Because the brain has high aerobic activity, requiring about 20 times more energy than the rest of the body by weight Kety, , it is highly vulnerable to conditions stemming from impaired energy production. A resting cortical neuron consumes 4.
Evidence from post-mortem Kato et al. Studies are also emerging providing evidence that mitochondria-mediated mechanisms are related to depressive symptoms reviewed in Castren, ; Tobe, ; Shimamoto and Rappeneau, ; Petschner et al. Mitochondria could play a role in the dampened plasticity associated with depression. Depression is associated with abnormalities in intracellular second messenger signal transduction cascades resulting from 5HT and NE receptor activation Perez et al.
These observations can be related to mitochondrial dysfunction because ATP is needed for the activation of downstream signaling following the binding of neurotransmitters to receptors Moretti et al.
ATP is also necessary to attend to the energy demands of vesicle transport and neurotransmitter release reviewed in Vos et al. Furthermore, patients with mitochondrial diseases or mitochondrial DNA mtDNA mutations and polymorphisms often present symptoms characteristic of mood disorders Suomalainen et al. Higher rates of mitochondrial biogenesis are needed for neuronal differentiation Calingasan et al.
There have been many observations of links between mtDNA and depression. As mentioned above, depression is a heterogeneous disorder, with several different symptom profiles, and genetic background contributes to its development Lesch, However, not all patients who have the same mitochondrial gene mutations develop depressive symptoms, indicating a genetic and non-genetic interplay of factors Koene et al.
Similarly, in leukocytes of depressed patients, mtDNA copy number variates were significantly lower than in control subjects, and mtDNA oxidative damage was increased Chang et al. Interestingly, oxidized mtDNA activates pro-inflammatory cytokines Adzic et al. Variations in mtDNA have also been shown to cause cognitive impairments in mice Sharpley et al. Beyond these general linkages between mtDNA and depression, recent research has implicated a number of specific mitochondrial genes in depression.
This topic has been reviewed in detail recently Petschner et al. A recent systematic assessment using mitochondrial PCR array profiling identified 16 genes that were differentially expressed in the dorsolateral prefrontal cortex of post-mortem brains from depressed patients compared to control subjects Wang and Dwivedi, The identified genes are ones known to govern oxidative stress and neuronal ATP levels, suggesting for the first time that mitochondrial genes might be altered in tissue samples from human patients.
Similarly, the mitochondrial ATP6V1B2 gene has been implicated in depression, possibly through its effects on neurotransmission and receptor-mediated endocytosis Petschner et al. Less direct evidence comes from observations that mice with mutations of the POLG gene, which encodes a subunit of mtDNA polymerase, exhibit depression-like symptoms Kasahara et al.
This polymorphism is also associated with high levels of homocysteine, which has been related to hippocampal volume and depression Moustafa et al.
These examples point to an intriguing link between mtDNA or gene expression and depression, though more work needs to be done in this area, particularly to identify gene alterations in tissue from human patients. There have been many studies indicating the involvement of the oxidative phosphorylation OXPHOS pathway in depression. In addition, proteomic studies using different animal models of depression have revealed alterations in specific proteins involved in OXPHOS and also confirmed the effect of antidepressant treatment in the expression of these proteins reviewed in Carboni, In depressed patients, most of the differentially expressed proteins are involved in cellular assembly, organization, function, and maintenance, as well as cardiovascular system development and function, but they are mainly related to deregulation of energy metabolism pathways Martins-de-Souza et al.
In addition, 60 non-synaptic mitochondrial-related proteins were upregulated whereas three were downregulated. When looking at samples from the dorsolateral prefrontal cortex, which shows reduced activation and volume in patients with depression Drevets et al.
Two other proteomic studies showed that several proteins involved in energy metabolism, such as carbonic anhydrase and aldolase C, were increased in the frontal cortex Johnston-Wilson et al. These results are consistent with PET findings of a reduction in cerebral glucose metabolism in the brains of depressed patients Baxter et al. Similarly, PET studies also revealed that depressed patients had reduced blood flow and bioenergetic metabolism in the prefrontal cortex Drevets et al.
Psychiatric disorders almost always have overlapping symptoms, which might reflect common mechanisms when compared against controls. An interesting study addressing this issue showed that patients with major depression that included psychosis had more differentially expressed proteins associated with energy metabolism, whereas patients with depression without psychosis had changes in proteins associated with cell growth and maintenance, although Subtle differences in proteome fingerprints may become useful biomarkers that could be used to stratify patients with different symptoms profiles and to formulate effective personalized treatment plans.
Proteomic studies support the view that mitochondrial dysfunction is one of many important factors involved in depression, and may identify novel pathogenic mechanisms of psychiatric disorders.
That alterations in mitochondria bioenergetics pathways contributed to the pathophysiology of depression also raise the possibility of developing mitochondrial biomarkers that can illustrate a better therapeutic approach to the treatment of depression. However, this field is still undeveloped and additional studies are needed characterizing specific mitochondrial dysfunctions in depression in relation to therapeutic response to antidepressants, or to evaluate the possibility of identifying mitochondrial drug targets that could be used to develop novel antidepressant drugs Klinedinst and Regenold, Several lines of research have confirmed that depression is associated with lower than normal levels of ATP production.
For example, brain levels of ATP are generally lower in the brains of depressed patients compared to control subjects Moretti et al. This may be related to the dampened neuronal plasticity and impaired hippocampal neurogenesis thought to be operative in depression Caruncho et al.
Other researchers have found changes in ATP in depression in areas outside the brain. A correlation was found between altered biochemistry and depression rating scale scores further evidencing the relationship between mitochondrial dysfunction and psychopathology.
In peripheral blood mononuclear cells, ATP turnover-related respiration was lowered in depressed patients compared to age-matched controls, as well as routine and uncoupled respiration and coupling efficiency Karabatsiakis et al.
Moreover, ATP-binding cassette transporters, which utilize the energy of ATP, are also altered in depressed patients and single nucleotide polymorphisms in the gene that codes for these transporters may be indicators of severity of the disorder and patient responsiveness to antidepressants Lin et al. Decreased ATP production has also been observed in preclinical animal models of depression. Female rats displaying anhedonia i.
In another study, fluoxetine restored sucrose preference, and normalized ATP synthesis rate and mitochondrial respiratory control in the raphe nucleus after 18 days of chronic unpredictable stress Wen et al. Another study using the chronic mild stress paradigm revealed that mice with decreased sucrose preference and increased immobility in the tail suspension test i.
Mitochondria are the primary source of ROS, which under normal conditions play important roles in cell signaling and homeostasis. ROS are produced in the OXPHOS pathway; however, in normal physiological conditions, mitochondria create protective factors that can neutralize harmful free radicals Petschner et al.
For example, there is a mitochondrial matrix thiol system that has an important role in antioxidant protection Murphy, In the ETC, complexes donate electrons to oxygen producing radicals like superoxide and peroxidases, and high levels of such radicals and oxidative stress cause damage to lipids, enhance DNA breaks, and oxidize nuclear and mtDNA Tobe, ; Czarny et al. Lower levels of ROS also play a role in normal cellular functioning, such as differentiation of cells, tissue regeneration, redox biology, and promoting adaptation to environmental changes Vakifahmetoglu-Norberg et al.
The production of highly reactive free radicals is increased when premature leakage of electrons to oxygen occurs in the ETC, increasing oxidative stress. Oxidative stress could be the cause or consequence of damage to mitochondria and mtDNA Xie et al. In fact, ATP reduction and its relation to oxidative stress have been linked not only to depression detailed below , but also to psychotic disorders see Chouinard et al. Several papers have reported links between oxidative stress and depression.
Ben-Shachar and Karry reported an increase in oxidative damage and alterations in ETC complex I in the prefrontal cortex of depressed patients.
Other researchers noted decreased levels of antioxidants and antioxidant enzymes in depression and related these changes to deficits in cognition Anderson, In an immobilization stress preclinical model of depression, in which animals were restrained for 6 h a day, levels of the cellular antioxidant glutathione were reduced by The authors speculated that lipid peroxidation could cause mitochondrial dysfunction by damaging membranes and causing excitotoxicity, which could be potentiated by increased production of reactive molecules Braughler and Hall, or decreased antioxidant levels.
In the olfactory bulbectomy model of depression, glutathione levels were also decreased whereas ROS superoxide, nitric oxide NO , and lipid hydroperoxide levels were increased in mice Holzmann et al.
As previously mentioned, the effect of 21 days of environmental stress i. The authors reported that mitochondrial activity of ETC complexes I—III were significantly decreased after just 7 days of restraint stress 6 h per day ; however, there was no difference in complex IV and no stress-induced decreases in oxygen consumption throughout the day period.
They speculated that mitochondrial dysfunction was a result of overproduction of NO, as an accumulation of NO metabolites was found in the brain tissue.
Similarly, 40 days of chronic variable stress decreased sucrose preference as well as inhibited ETC complexes I, II, and IV in the cerebral cortex and cerebellum of rats Rezin et al. Interestingly, increased expression of proteins related to mitochondrial import and transport in the OXPHOS pathway was also seen in a preclinical mouse model of anxiety, a disorder that is highly comorbid with depression Filiou et al.
Moreover, in this model, the expression of enzymes involved in catalyzing glycolysis pathway reactions was also dysregulated. The mechanisms by which environmental stress negatively impacts the brain are still not fully understood. However, there is evidence that free-radicals such as NO cause rapid damage to certain cell macromolecules that are involved in the ETC system, which in turn will decrease production of ATP and may be implicated in cytotoxic effects in the central nervous system Cleeter et al.
Antidepressant treatment improves oxidative stress parameters in patients with depression. For example, a higher serum total oxidant status and a lower serum total antioxidant capacity in depressed patients were normalized after 42 days of antidepressant treatment Cumurcu et al.
Similar findings have been reported in animal models of depression. Furthermore, in the chronic mild stress paradigm, lamotrigine, aripiprazole, and escitalopram all normalized glutathione and glutathione peroxidase activity in rat cortical regions Eren et al. Lipid peroxidation in the cortex and plasma was increased by chronic mild stress, but also reversed by the same three treatments.
A similar study revealed that venlafaxine can reverse chronic mild stress-induced decreases in glutathione peroxidase activity and vitamin C, and increases in lipid peroxidation and NO in the rat cortex Eren et al. Moreover, unpredictable stress in mice resulted in increased open field test exploration along with decreased liver glutathione, superoxide dismutase, and total antioxidant capability, which was reversed by the traditional Chinese medicine, Shudihuang, in a dose-dependent manner Zhang et al.
A further link between ROS and depression has been suggested by recent work focused on the extracellular matrix protein reelin. Reelin has been linked to depression in preclinical models of depression: Interestingly, a subpopulation of reelin containing cells also coexpress nNOS, and the percentage of neurons coexpressing both markers is specifically decreased in the subgranular zone and molecular layer of the dentate gyrus in HRM Romay-Tallon et al.
As reelin secretion by neurons in the subgranular zone may be involved in regulating the maturation of adult hippocampal newborn neurons Lussier et al. We interpreted these results as being indicative of profound excitotoxicity in dentate gyrus neurons after chronic exposure to stress hormones to a degree that produces depression-like behavior Romay-Tallon et al.
Nitric oxide and other ROS inhibit mitochondrial 2-oxoglutarate dehydrogenase giving rise to increased levels of glutamate, which eventually leads to glutamate excitotoxicity and cell death Weidinger et al. The reelin—nNOS connection should receive more experimental attention, as a number of reports indicate that alterations in reelin expression within the dentate gyrus may result in deficient maturation of newborn granule neurons and dampened hippocampal plasticity, and may represent a key event in the pathophysiology of depression reviewed in Caruncho et al.
There is also a key link with inflammation to consider in the context of these experiments. Many studies support the idea that inflammatory processes are involved in depression, and in fact targeting of inflammatory cytokines to reduce depression symptoms is a very active area of research recently reviewed by Shariq et al.
Studies have shown that pro-inflammatory cytokines alter ETC complexes and complex associated enzymes Samavati et al. In mice, the injection of lipopolysaccharide, which induces strong immune responses and secretion of pro-inflammatory cytokines, significantly increased depression-like behavior in the sucrose preference and forced swim tests, and decreased ATP levels and mitochondrial membrane potential in the hippocampus Chen et al.
Alterations in several components of the immune system, and in inflammatory markers, have also been observed in animals with low or null reelin expression Green-Johnson et al. We have reported that these animals not only are quite susceptible to the depressogenic effects of repeated CORT Lussier et al.
In fact, alterations in oxidative stress in lymphocytes have been clearly demonstrated in depression Szuster-Ciesielska et al. Following up this line of thought, we have recently demonstrated that peripheral injections of the anti-inflammatory drug etanercept which is unable to cross the blood—brain—barrier not only rescues the depression-like behavior induced by repeated CORT but also normalizes the neurochemical phenotype of reelin expressing cells in the hippocampal dentate gyrus.
We speculated that both peripheral and secondary central actions may be operative in the antidepressant effects of etanercept injections Brymer et al. It seems clear that additional studies would be required to determine the connection between reelin, oxidative stress, and inflammation in depression, not only to determine how these factors may be an important component of the pathophysiology of depression, but also to evaluate them as possible targets to develop novel antidepressant drugs.
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 formation and morphology of cristae on the inner membrane, which regulate mitochondrial metabolism, may require fusion machinery as a loss of such machinery results in decreased metabolism McBride et al.
Abnormal cell structure and function could result in alterations in synaptic signaling and neural circuits and vice versa Kaidanovich-Beilin et al. Excessive glutamatergic activation of NMDA receptors was shown to increase ROS levels and alter mitochondrial membrane polarity, which led to elevated apoptosis rates in cardiomyocytes, possibly as a result of increased calcium ion influx Gao et al. Mitochondria are present at synapses and responsive to synaptic stimulation McBride et al.
As the hippocampus is highly vulnerable to the depressogenic effects of chronic stress, it is likely that hippocampal mitochondria behave abnormally in depressed patients. For example, the clustering of mitochondria in dendritic spines in response to neural activity may be altered Li et al. Glucocorticoid receptors GRs are also highly prevalent in the hippocampus. These receptors are activated when stress hormone levels are high, such as during periods of chronic stress. In the hippocampus, chronic stress altered the phosphorylation of mitochondrial GRs, whereas in the prefrontal cortex, chronic stress significantly increased mitochondrial GR levels Adzic et al.
Mitochondria are also involved in apoptosis through the extrinsic pathway, in which the death-inducing signaling complex is formed, leading to activation of caspase-8 and then downstream caspases that target substrates leading to programmed cell death Vakifahmetoglu-Norberg et al. Other proteins such as K-Ras or BH3 interacting domain death agonist can also induce cell death when activated by caspases by translocating to mitochondria, where they trigger the release of the executioner caspases Bivona et al.
It is important to note that the effect of stress on mitochondrial function may depend on the nature of the stressor or period of chronicity.
Although chronic stress and high levels of circulating stress hormones are a clear risk factor for depression Gibbons and McHugh, ; Holsboer, ; Parker et al. For example, the effects of the stress hormone CORT on depression-like behavior in rodent models depend on the dose and time period of administration: This is consistent with the effects of stress hormones on mitochondria.
Glucocorticoids can translocate to mitochondria, where they inhibit the release of cytochrome c and decrease apoptosis Du et al. However, this is dependent on the level of glucocorticoids present in the tissue. Similarly, inhibiting mitochondrial protein synthesis completely impairs neuronal differentiation, but inhibiting ATP synthetase alone does not affect neurogenesis Vayssiere et al.
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. While yeast do not have easily measured mood swings, the intrinsic effects of various drugs on cell machinery can be studied, at least at the discovery stage, with much less effort. In watching video footage of mitochondrial motions it is perhaps difficult to attribute the full dynamic behavior of mitochondria to a few comparatively miniscule molecular motors, particularly motion within a fairly constrained skeletal meshwork.
If mitochondria have other tricks to move about the cell, perhaps riding action potential waves, seeding cytoskeletal propulsion like Listeria bacteria, or otherwise directing asymmetric ion pumping or flow across their membranes, they, rather then their neuron hosts, might be seen as the prime movers in the brain.
Much of the presumed action of various drugs on mitochondria is through neurotransmitter systems, in particular serotonin and dopamine. These signals ultimately cause calcium influx on both sides of the synapse, and subsequently mitochondria are scuttled to assist in the mopping and redistribution.
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. Your feedback will go directly to Science X editors.
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Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression
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, ;.