Photobiomodulation (PBM) is a non-invasive strategy to enhance cognitive function, yet the effects of stimulation frequency remain unclear. We applied pulsed 810 nm PBM at 5 Hz or 40 Hz to the frontal cortex of adult rats, and 40 Hz PBM to aged rats. In young adults, both stimulation frequencies enhanced cognitive flexibility, and in aged rats 40 Hz PBM improved learning speed. In terms of brain changes, we studied cytochrome c oxidase (CCO) activity, c-Fos expression and protein levels. We observed a decrease in the prefrontal CCO activity in adults, and an increase in prefrontal c-Fos expression, both with 40 Hz. Regarding protein levels in young rats, 5 Hz PBM reduced pERK expression in the hippocampus and p38 in the prefrontal cortex, while regulating interleukins and cytokines in these regions. Additionally, 5 Hz upregulated Synapsin-I expression in both the prefrontal cortex and hippocampus, and increased PSD-95 levels selectively in the hippocampus, highlighting its role in synaptic plasticity and memory consolidation. Notably, 5 Hz also increased GFAP expression in both regions, and selectively upregulated NF-κB expression. 40 Hz PBM reduced pERK expression in the hippocampus and p38 in the prefrontal cortex, also modulating interleukins and cytokines in these areas. Additionally, 40 Hz increased p38 expression in the hippocampus and reduced p53 and BAX levels in the prefrontal cortex. Also, 40 Hz upregulated Synapsin-I in both regions and increased PSD-95 expression in both the prefrontal cortex and hippocampus. As observed with 5 Hz, 40 Hz also elevated GFAP expression in both regions. In aged rats, PBM reduced Iba-1 in prefrontal cortex and hippocampus, enhanced NeuN in prefrontal cortex, and decreased p38 and BCL-2 in the hippocampus. Collectively, these results demonstrate frequency-dependent modulation of neuroinflammation, synaptic plasticity, and apoptosis, while highlighting the beneficial effects of 40 Hz PBM in aged subjects, supporting PBM as a targeted approach to improve cognitive function across the lifespan.

Aging is associated with progressive cognitive decline and increased vulnerability to anxiety-related behaviors, partly due to mitochondrial dysfunction and reduced neuronal metabolic capacity. Transcranial photobiomodulation (tPBM) has emerged as a non-pharmacological intervention capable of stimulating mitochondrial cytochrome-c-oxidase and enhancing brain function. This study evaluated the effects of tPBM on anxiety-like behavior, spatial learning, and regional brain oxidative metabolism in adult and old female Wistar rats. Forty rats (10 or 18 months old) received 12 consecutive days of tPBM (810 nm; 20 J/cm²; 40 mW) or SHAM stimulation. Behavioral performance was assessed using the Elevated Zero Maze (EZM) and Morris Water Maze (MWM), followed by quantitative cytochrome-c-oxidase (CCO) histochemistry to evaluate regional brain metabolic activity.tPBM significantly reduced anxiety-like behavior in both age groups, evidenced by lower anxiety index scores and increased time in open arms in the EZM. In adult rats, tPBM improved spatial learning and memory performance in the MWM, whereas effects were limited in old animals. Analysis of CCO activity revealed increased metabolic activity in prefrontal, hippocampal, striatal, and somatosensory regions in adult rats versus the SHAM group. In old rats, higher levels of CCO activity as compared to an age-matched SHAM group were observed in the primary motor cortex, nucleus accumbens core, CA1, and somatosensory cortex. These findings suggest age-dependent responsiveness to tPBM, with greater behavioral and metabolic effects in adult compared with aged females.Overall, tPBM decreased anxiety-like behavior and selectively improved cognitive performance while enhancing metabolic activity in key brain regions such as the prefrontal cortex, dorsal hippocampus, and motor control regions. These results support tPBM as a promising neuromodulatory approach during aging and highlight the need for sex-specific and protocol-standardized research.

Photobiomodulation (PBM) is an innovative non-invasive light-based technique that uses wavelengths around red to infrared light to stimulate neural activity. Literature has addressed PBM’s effectiveness in healthy adult subjects, in several neurological conditions, and also in younger populations. However, there is still a lack of both preclinical and clinical studies that evaluate its safety during early developmental stages, when the brain is still maturing. We explored safety of PBM (810 nm) in young male Wistar rats by examining astrocytes and microglia cells thought GFAP and Iba1 immunohistochemistry, as well as the expression of pro-inflammatory cytokines (Interleukin-6, interleukin-1β and tumour necrosis factor α) through quantitative PCR, both in prefrontal cortex and hippocampus. Under the tested parameters and time point, PBM did not induce detectable glial reactivity or pro-inflammatory cytokine expression. This research highlights the potential use of 810 nm-PBM in the developing brain, providing preliminary evidence that this technique does not induce a neuroinflammatory response, representing an important first step to verifying the beneficial use of this technique without risks in paediatric and adolescence populations. More research is necessary to confirm the safety of PBM for different conditions and employing diverse parameters.

Aging is marked by a progressive decline in cognitive and behavioral functions, underscoring the need for innovative therapeutic strategies. Photobiomodulation (PBM) therapy has emerged as a non-invasive technique that enhances mitochondrial function and supports neural plasticity. In this study, 9-month-old Wistar rats received automatic transcranial PBM over the prefrontal cortex for 11 consecutive days (12 min/day, 810 nm). Behavioral assessments included anxiety-like behavior, motor activity, spatial memory, and cognitive flexibility. Neurobiological analyses focused on cytochrome c oxidase (CCO) activity and c-Fos expression across the limbic system. The PBM group demonstrated improvements in spatial memory with significant enhancements in cognitive flexibility. No significant differences were observed in anxiety-like behavior or locomotor activity. At the neurobiological level, PBM induced a reduction in CCO activity across several regions of the limbic-cortical network, including the prefrontal cortex, septum, CA1 and CA3 hippocampal subfields, and lateral mammillary nuclei, which are areas implicated in memory and executive functions. Additionally, an increase in c-Fos expression was detected in the dorsal dentate gyrus, a key region for memory encoding and retrieval. These results delineate the behavioral and neurobiological profile of transcranial PBM in middle-aged rats, highlighting its ability to modulate cognitive performance and brain activity in memory-related circuits without affecting anxiety levels or locomotor activity. Further studies are warranted to refine and standardize stimulation parameters, assess the durability of the effects over time, and investigate possible sex-specific responses. Particular attention should be given to validating automated PBM systems, which offer consistent and reproducible delivery.

PURPOSE:Metabolic dysfunction-associated steatohepatitis (MASH) is a prevalent disease caused by high fat and high cholesterol intake, which leads to systemic deterioration. The aim of this research is to conduct a psychobiological exploration of MASH in adult male rats. METHODS:Subjects who were administered a high-fat and high-cholesterol diet for 14 weeks. Then, we assessed the acoustic startle response and alertness through the prepulse inhibition paradigm as well as the associative learning by the use of the passive avoidance test. Also, we explored the astrocyte density in the prefrontal cortex and hippocampus. RESULTS:Our results showed that, whereas the MASH group did not display an impaired associative learning, a lower exploration rate was found in this group. Moreover, a reduced prepulse inhibition was found in these subjects in the case of the weaker and closer-to-the-stimulus prepulse, which indicates a mild alteration in this process. No differences were found in astrocyte density in the MASH group in comparison with controls. CONCLUSION:MASH seems to be linked with cognitive dysfunction. Further research is needed to elucidate the pathway involved in this disease and its underlying mechanism, as well as the potential implication in human health.

INTRODUCTION:The escalating prevalence of obesity presents a multifaceted challenge involving genetic, environmental, and behavioral factors, with significant public health implications. Photobiomodulation (PBM) may positively influence metabolic activities in adipose cells and regulate inflammation, potentially impacting obesity. METHODS:A systematic review and meta-analysis were conducted to assess the effects of transabdominal PBM treatments in preclinical and clinical obesity studies, covering a range of physical, psychological, and physiological variables. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Following the inclusion and exclusion criteria, a total of 24 studies, comprising 1041 patients, and 100 mice were incorporated. R software was employed for conducting meta-analyses, and calculating effect sizes between experimental and control groups. RESULTS:In human models, significant discrepancies were revealed in waist circumference (Z = -2.16; p = 0.031), hip circumference (Z = 2.11; p = 0.035), insulin levels (Z = 2.11; p = 0.035), and triglycerides (Z = -2.4674, p = 0.0136). In animal models, significant differences were observed in epididymal adipocyte area (Z = -5.6930; p < 0.0001), triglycerides (Z = -2.0254; p = 0.04848), and glucose area under the curve (AUC; Z = -6.4112; p < 0.0001). CONCLUSIONS:This study underscores the necessity of considering diverse wavelengths in PBM research, particularly within the realm of obesity, and emphasizes the imperative for further investigations to comprehensively elucidate PBM mechanisms and applications. The exploration of innovative therapeutic approaches unfolds novel avenues in the pursuit of comprehensive strategies to address obesity and its underlying determinants.

Photobiomodulation (PBM) uses red and near-infrared light to stimulate biological processes through cytochrome c oxidase (CCO) activation, enhancing ATP synthesis and neuroprotection. This study evaluates the PBM effects on spatial working memory (WM) and cellular mechanisms in healthy adult male rats, focusing on CCO activity, c-Fos, and synaptogenesis-related proteins. PBM (810 nm, 40 Hz, 20 J cm-2) is applied for five consecutive days (PBM-C) or five alternating days (PBM-A). PBM improves spatial WM in both groups compared to controls. CCO activity decreases in the prefrontal and retrosplenial cortex, as well as in the hippocampus, suggesting more efficient energy use during cognitive tasks. PBM increases c-Fos expression in the prefrontal and parietal cortex, reflecting heightened neuronal activity. Synapsin-I levels rise in the prefrontal cortex for both protocols, while PBM-C increases PSD-95 in the hippocampus. GFAP expression decreases in cortical regions with both protocols, while PBM-C increases it in the prefrontal cortex. These findings suggest that PBM PBM-C enhances prefrontal and hippocampal synapses, potentially underlying observed WM improvements. This study highlights the PBM potential in modulating CCO activity and synaptic plasticity, providing a basis for identifying effective schedules and targets for WM preservation and treatment.

This research aims to examine the influence of human skull bone thickness and density on light penetration in PBM therapy across different wavelengths, focusing on how these bone characteristics affect the absorption of therapeutic light. Analyses explored the effect of skull bone density and thickness on light penetration in PBM, specifically using Low-Level Laser Therapy (LLLT) for efficacy prediction. Measurements of bone thickness and density were taken using precise tools. This approach emphasizes LLLT's significance in enhancing PBM outcomes by assessing how bone characteristics influence light penetration. The study revealed no significant correlation between skull bone density and thickness and light penetration capability in photobiomodulation (PBM) therapy, challenging initial expectations. Wavelengths of 405 nm and 665 nm showed stronger correlations with bone density, suggesting a significant yet weak impact. Conversely, wavelengths of 532 nm, 785 nm, 810 nm, 830 nm, 980 nm, and 1064 nm showed low correlations, indicating minimal impact from bone density variations. However, data variability (R2 < 0.4) suggests that neither density nor thickness robustly predicts light power traversing the bone, indicating penetration capability might be more influenced by bone thickness at certain wavelengths. The study finds that the effectiveness of photobiomodulation (PBM) therapy with bone isn't just based on bone density and thickness but involves a complex interplay of factors. These include the bone's chemical and mineral composition, light's wavelength and energy dose, treatment duration and frequency, and the precise location where light is applied on the skull.

Photobiomodulation (PBM), an emerging and non-invasive intervention, has been shown to benefit 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 effect 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 differences 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 differences in CCO activity across the limbic system, suggesting that a combination of lights of the spectrum may be relevant.

Aging is a multifactorial biological process that may be associated with cognitive decline. Photobiomodulation (PBM) is a non-pharmacological therapy that shows promising results in the treatment or prevention of age-related cognitive impairments. The aim of this review is to compile the preclinical and clinical evidence of the effect of PBM during aging in healthy and pathological conditions, including behavioral analysis and neuropsychological assessment, as well as brain-related modifications. 37 studies were identified by searching in PubMed, Scopus, and PsycInfo databases. Most studies use wavelengths of 800, 810, or 1064 nm but intensity and days of application were highly variable. In animal studies, it has been shown improvements in spatial memory, episodic-like memory, social memory, while different results have been found in recognition memory. Locomotor activity improved in Parkinson disease models. In healthy aged humans, it has been outlined improvements in working memory, cognitive inhibition, and lexical/semantic access, while general cognition was mainly enhanced on Alzheimer disease or mild cognitive impairment. Anxiety assessment is scarce and shows mixed results. As for brain activity, results outline promising effects of PBM in reversing metabolic alterations and enhancing mitochondrial function, as evidenced by restored CCO activity and ATP levels. Additionally, PBM demonstrated neuroprotective, anti-inflammatory, immunomodulatory and hemodynamic effects. The findings suggest that PBM holds promise as a non-invasive intervention for enhancing cognitive function, and in the modulation of brain functional reorganization. It is necessary to develop standardized protocols for the correct, beneficial, and homogeneous use of PBM.

BACKGROUND:Novel flavors elicit a cautious neophobic response which is attenuated as the flavor becomes familiar and safe. The attenuation of neophobia reveals the formation of a safe memory. Previous lesion studies in rats have reported that basolateral amygdala integrity is required for taste neophobia, but not neophobia to flavor, i.e., taste linked to an odorous component. Accordingly, immunohistochemical analyses show that novel tastes induced higher basolateral amygdala activity when compared to familiar ones. However, a different role of basolateral amygdala in flavor attenuation of neophobia is suggested by lesion studies using a vinegar solution. Studies assessing basolateral amygdala activity during flavor attenuation of neophobia are lacking. Thus, we quantified cytochrome oxidase as an index of basolateral amygdala activity along the first and second vinegar exposures in order to assess flavor neophobia and attenuation of neophobia. METHODS:We exposed adult male Wistar rats either once or twice to a 3% cider vinegar solution or water, and compared the basolateral amygdala, piriform cortex and caudate putamen brain metabolic activity using cytochrome c-oxidase histochemistry. RESULTS:We found increased flavor intake and cytochrome c-oxidase histochemistry activity during the second exposure in basolateral amygdala, but not in the piriform cortex and caudate/putamen. CONCLUSIONS:The main finding of the study is that BLA metabolic activity was higher in the group exposed to a familiar vinegar solution than in the groups exposed to either water or a novel vinegar solution.

Spatial memory is responsible for encoding spatial information to form a path, storing this mental representation, and evaluating and recovering spatial configurations to find a target location in the environment. It is mainly supported by the hippocampus and its interaction with other structures, such as the prefrontal cortex, and emerges in rodents around postnatal day (PND) 20. Sex differences in spatial tasks have been found in adults, with a supposedly better performance in males. However, few studies have examined sex differences in orien-tation throughout postnatal development. This study aimed to analyse the performance of juvenile (PND 23) male (n = 18) and female (n = 21) Wistar rats in a spatial reference memory task in the Morris water maze (MWM) with two different training regimes in the acquisition phase, and their subjacent metabolic brain activity. Based on sex, subjects were assigned to two different groups: one that performed four learning trials per day (n = 9 males and n = 8 females) and the other that was submitted to two trials per day (n = 9 males and n = 13 females). After the behavioural protocols, metabolic activity was evaluated using cytochrome c oxidase histo-chemistry. Results showed no metabolic brain or behavioural differences in the four-trial protocol performance, in which both sexes reached the learning criterion on the fourth day. By contrast, the two-trial protocol revealed an advantage for females, who reached the learning criterion on day four, whereas males needed more training and succeeded on day six. The female group showed lower metabolic activity than the male group in the cingulate and prelimbic cortex. These results suggest a faster consolidation process in the female group than the male group. Further research is needed to understand sex differences in spatial memory at early stages.

Sex differences have been found in allocentric spatial learning and memory tasks, with the literature indicating that males outperform females, although this issue is still controversial. This study aimed to explore the behavior of male and female rats during the habituation and learning of a spatial memory task performed in the Morris Water Maze (MWM). The study included a large sample of 89 males and 85 females. We found that females searched slightly faster than males during habituation with a visible platform. During learning, both male and female rats decreased the latency and distance traveled to find the hidden platform over the days, with males outperforming females in the distance traveled. Females swam faster but did not find the platform earlier, suggesting a less directed navigational strategy. Both sexes increased time spent in the target zone over the days, with no sex differences. Although females swam more in the periphery during the first days of the task, both sexes decreased the time spent in this area. Finally, only males increased swimming in the pool's center over the days, spending more time than females in this area across the entire training. In conclusion, we need to register several variables in the MWM and analyze path strategies to obtain more robust results concerning sex differences. Research on spatial learning should include both sexes to achieve a more equitable, representative, and translational science.

Successful spatial cognition involves learning, consolidation, storage, and later retrieval of a spatial memory trace. The functional contributions of specific brain areas and their interactions during retrieval of past spatial events are unclear. This systematic review collects studies about allocentric remote spatial retrieval assessed at least two weeks post-acquisition in rodents. Results including non-invasive interventions, brain lesion and inactivation experiments, pharmacological treatments, chemical agent administration, and genetic manipulations revealed that there is a normal forgetting when time-periods are close to or exceed one month. Moreover, changes in the morphology and functionality of neocortical areas, hippocampus, and other subcortical structures, such as the thalamus, have been extensively observed as a result of spatial memory retrieval. In conclusion, apart from an increasingly neocortical recruitment in remote spatial retrieval, the hippocampus seems to participate in the retrieval of fine spatial details. These results help to better understand the timing of memory maintenance and normal forgetting, outlining the underlying brain areas implicated.