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Heat color map of Pearson’s r values for each pairwise correlation between two ROIs in the sham group. Red indicates positive inter-regional correlations and blue indicates negative correlations. * indicates a p-value < 0.05. ** indicates a p-value < 0.01. *** indicates a p-value < 0.001.
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Introduction
This is the first study mapping the duration of action of in vivo photobiomodulation (PBM) on cytochrome-c-oxidase (CCO). In cellular bioenergetics, CCO is the terminal rate-limiting enzyme in the mitochondrial electron transport chain, which catalyzes oxygen utilization for aerobic energy production. PBM using transcranial infrared la...
Citations
... Interestingly, the CCO enzyme is the major intracellular photoceptor that can absorb specific wavelengths, leading to molecular and cellular modifications [1,12]. The CCO enzyme contains a heme and copper centres with red (620-680 nm) or infrared (760-825 nm) spectral absorption peaks [13]. ...
... The stimulation of CCO also induces the replication of mitochondrial DNA, thereby activating early genes [4,13]. Therefore, PBM emerges as a novel approach to modulating bioenergetics in the brain [12,16]. ...
... When applying only the NIR spectrum, there was also an increase in brain metabolic activity in male and female rats in some areas functionally interconnected with the prefrontal cortex [36]. In this line, it has been shown that the effect observed in the CCO activity due to PBM treatment is not limited to the target area stimulated, but instead spreads over several brain regions interconnected with the target [12,37,38]. However, it is important to note that no statistical differences were found between treatments, although there was an increase in 6 brain areas after 810-nm PBM treatment, and in 9 brain areas after a combination of waves. ...
Photobiomodulation (PBM), an emerging and non-invasive intervention, has been shown to beneft the nervous system by
modifying the mitochondrial cytochrome c-oxidase (CCO) enzyme, which has red (620–680 nm) or infrared (760–825 nm)
spectral absorption peaks. The efect of a single 810-nm wavelength with a combination of 810 nm and 660 nm lights in the
brain metabolic activity of male and female rats was compared. PBM, with a wavelength of 810 nm and a combination of
810 nm and 660 nm, was applied for 5 days on the prefrontal cortex. Then, brain metabolic activity in the prefrontal area,
hippocampus, retrosplenial, and parietal cortex was explored. Sex diferences were found in cortical and subcortical regions,
indicating higher male brain oxidative metabolism, regardless of treatment. CCO activity in the cingulate and prelimbic area,
dentate gyrus, retrosplenial and parietal cortex was enhanced in both treatments (810 +660 nm and 810 nm). Moreover,
using the combination of waves, CCO increased in the infralimbic area, and in CA1 and CA3 of the hippocampus. Thus,
employment of a single NIR treatment or a combination of red to NIR treatment led to slight diferences in CCO activity
across the limbic system, suggesting that a combination of lights of the spectrum may be relevant.
Background: This study addresses the urgent need for effective alternatives to treat major depressive disorder (MDD) in patients who do not respond to conventional therapies Transcranial photobiomodulation therapy (tPBM) shows promise by enhancing mitochondrial function and reducing oxidative stress, as demonstrated in the chronic mild stress (CMS) rat model.
To analyze the impact of tPBM with two wavelengths (red and infrared) on behavioral and biological parameters related to MDD in a CMS model.
Methods: Male Wistar rats were subjected to CMS for five weeks and categorized into resilient (CMS-R) and susceptible (CMS-S) groups using the sucrose consumption test (SCT). The CMS-S group received tPBM treatment (600nm and 840nm) for five weeks. Biological measures included lipid damage (TBARS), antioxidant defense (TEAC), mitochondrial complex IV activity (CCO), and nitric oxide (NO) concentration in the prefrontal cortex and blood were measured.
Results: As expected, post-tPBM treatment (both red and infrared groups) exhibited increased sucrose consumption compared to the sham (Kruskal Wallis chi-squared=26.131; p<0.001). The red and infrared presented higher serum TEAC levels than the sham and control groups, but these effects did not reach statistical significance (p=0.306). In contrast, the red group showed lower peripheral TBARS levels (M = 9.50, SD = 2.87) than the sham group (M = 13.66, SD = 2.20) (p=0.0048); such effect was similar to the control non-stress group. The infrared group showed higher NO levels within the hippocampus than the sham group (Mean = 107.83; SD = 6.48, Dunn Test p = 0.0134) and higher prefrontal CCO activity levels than the red group (p=0.012), which was similar to the control non-stress group.
Conclusions: Our study demonstrated that tPBM using both red and infrared wavelengths significantly improved behavioral and biological parameters in the chronic mild stress (CMS) rat model. In particular, tPBM may offer therapeutic benefits by ameliorating oxidative stress and enhancing mitochondrial function, thereby presenting a promising alternative for the management of MDD.
Purpose of Review
Major depressive disorder (MDD) is a leading cause of disability worldwide; however, current treatments have inconsistent remission rates and burdensome side effects. In part, this may be due to the altered neurometabolism in MDD or the inability of current treatments to target mitochondrial function. Human and animal studies suggest key links between mitochondrial function and MDD. Transcranial photobiomodulation (t-PBM) is an innovative therapy for targeting the mitochondria via stimulating Complex IV of the mitochondrial respiratory changing (cytochrome c oxidase) and increasing adenosine triphosphate (ATP) synthesis and cerebral blood flow.
Recent Findings
In this review, we detail the application of t-PBM in both human and animal models of MDD and summarize the post-treatment changes in depressive symptoms and neurophysiology. Decreases in depression and increases in cerebral blood flow have been shown in clinical studies, while decreased depression behaviors and altered neurophysiology have been shown in pre-clinical studies after t-PBM.
Summary
Although limited by small sample sizes and heterogeneity across the methods employed (e.g., measures of depression, t-PBM parameters), animal and human studies suggest that t-PBM is promising in its ability to modulate brain activity and reduce MDD symptoms. Large randomized clinical trials and more methodological consistency are needed in future studies to further support the use of t-PBM for MDD symptoms and underlying pathophysiology.
There is growing evidence of mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism in bipolar disorder (BD). Older adults with BD exhibit greater decline in PFC-related neurocognitive functions than is expected for age-matched controls, and clinical interventions intended for mood stabilization are not targeted to prevent or ameliorate mitochondrial deficits and neurocognitive decline in this population. Transcranial infrared laser stimulation (TILS) is a non-invasive form of photobiomodulation, in which photons delivered to the PFC photo-oxidize the mitochondrial respiratory enzyme, cytochrome-c-oxidase (CCO), a major intracellular photon acceptor in photobiomodulation. TILS at 1064-nm can significantly upregulate oxidized CCO concentrations to promote differential levels of oxygenated vs. deoxygenated hemoglobin (HbD), an index of cerebral oxygenation. The objective of this controlled study was to use non-invasive broadband near-infrared spectroscopy to assess if TILS to bilateral PFC (Brodmann area 10) produces beneficial effects on mitochondrial oxidative energy metabolism (oxidized CCO) and cerebral oxygenation (HbD) in older (≥50 years old) euthymic adults with BD (N = 15). As compared to sham, TILS to the PFC in adults with BD increased oxidized CCO both during and after TILS, and increased HbD concentrations after TILS. By significantly increasing oxidized CCO and HbD concentrations above sham levels, TILS has the potential ability to stabilize mitochondrial oxidative energy production and prevent oxidative damage in the PFC of adults with BD. In conclusion, TILS was both safe and effective in enhancing metabolic function and subsequent hemodynamic responses in the PFC, which might help alleviate the accelerated neurocognitive decline and dysfunctional mitochondria present in BD.
