Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 6, 2024

The human retina is part of the central nervous system and can be easily non-invasively imaged with optical coherence tomography. While imaging may provide insights on system-related disorders such as schizophrenia, a typical challenge are confounders often present in schizophrenia which negatively impact retinal health. Here, we therefore aimed to investigate changes context common genetic variations conveying risk measured by polygenic scores. We used population data from UK Biobank, including White British Irish individuals without diagnosed estimated score for based newest genome-wide association study (PGC release 2022). hypothesized that greater susceptibility associated thinning, especially within macula. To gain additional mechanistic insights, conducted pathway-specific associations analyses, focusing gene pathways related schizophrenia. Of 65484 recruited, 48208 participants available matching imaging-genetic were included analysis whom 22427 (53.48%) female 25781 (46.52%) male. Our robust principal component regression results showed scores thinning while controlling confounding factors (b = −0.03, p 0.007, pFWER 0.01). Similarly, found specific neuroinflammation sets revealed significant self-contained 0.041 (reflecting level association), competitive 0.05 enrichment)). These go beyond previous studies suggesting relationship between manifested phenotypes. They indicate mirror reflecting complexities alterations observed connected an inherent predisposition neurodegenerative aspects condition. also suggest potential involvement neuroinflammatory pathway, indications overlap findings further this pathway high could contribute through acute-phase proteins structural retina.

Language: Английский

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Non-image-forming photoreceptors improve visual orientation selectivity and image perception

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Circadian Disruption in Glaucoma: Causes, Consequences, and Countermeasures

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)

Published: Dec. 3, 2024

This review explores the intricate relationship between glaucoma and circadian rhythm disturbances. As a principal organ for photic signal reception transduction, eye plays pivotal role in coordinating body's rhythms through specialized retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs). These are critical transmitting light signals to suprachiasmatic nucleus (SCN), central clock that synchronizes physiological processes 24-hour light-dark cycle. The delves into body clock, highlighting importance of retino-hypothalamic tract conveying information from eyes SCN. It underscores melanopsin ipRGCs absorbing initiating biochemical reactions culminate synchronization SCN's firing patterns with external environment. Furthermore, discusses local within eye, such as those affecting photoreceptor sensitivity, corneal thickness, intraocular fluid outflow. emphasizes potential optical coherence tomography (OCT) studying structural losses associated disruption. Glaucomatous damage is identified cause disruption, mechanisms including oxidative stress, neuroinflammation, direct RGCs. consequences disruption complex, systemic rhythms, sleep patterns, mood, metabolism. Countermeasures, implications management, proposed focus on strategies improve health balanced melatonin timing, daylight exposure, chronotherapeutic approaches. calls further research elucidate linking develop effective interventions address this aspect disease.

Language: Английский

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Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 27, 2025

Glutamate represents the dominant neurotransmitter that conveys light information to brain, including suprachiasmatic nucleus (SCN), central pacemaker for circadian system. The neuronal and astrocytic glutamate transporters are crucial maintaining efficient glutamatergic signaling. In SCN, nerve terminals from retina terminate on vasoactive intestinal polypeptide (VIP) neurons, which essential functions. To date, little is known about role of core clock gene, Bmal1, in neurotransmission signal various brain regions. aim this study was further elucidate Bmal1 SCN. We therefore examined spontaneous rhythmic locomotor activity, glial transporters, as well ultrastructure synapse between retinal ganglion cells (RGCs) SCN adult male Bmal1-/- mice. found deletion affects light-mediated behavior mice, decreases thickness vesicular (vGLUT1, 2) retina. Within immunoreaction vGLUT1, 2, (GLAST) VIP decreased while concentration elevated. At level, presynaptic were enlarged distance synaptic vesicles cleft increased, indicative a decrease readily releasable pool at excitatory synapses Bmal1-/-. Our data suggests transmission behavioral responses light.

Language: Английский

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Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness

Nature Mental Health, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Schizophrenia is associated with structural and functional changes in the central nervous system, including most distal part of it, retina. However, question whether retinal atrophy present before individuals develop schizophrenia or a secondary consequence disorder remains unanswered. Here we address this by examining association between polygenic risk scores for morphologies without diagnosis. We used population data 34,939 white British Irish from UK Biobank. Our robust regression results show that higher were thinner overall maculae, while controlling confounding factors ( b = −0.17, P 0.018). Similarly, found greater specific to neuroinflammation gene sets ganglion cell inner plexiform layers −0.10, self-contained 0.014, competitive 0.02). These provide new evidence genetic could predispose heightened neuroinflammatory responses. Over time, these responses contribute neurodegenerative processes such as thinning.

Language: Английский

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Lateral habenula astroglia modulate the potentiating antidepressant-like effects of bright light stimulation in intractable depression

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 23, 2025

Beside image vision, light plays a pivotal role in regulating diverse non-visual functions, including affective behaviors. Recently, bright stimulation (BLS) was revealed to be beneficial for treating non-seasonal depression, although its mechanism of action is not fully understood. We developed novel mouse model refractory induced through social isolation and chronic despair during the active (dark) phase animal, we have tested if antidepressant treatments, BLS, could protect against anxio-depressive-like behavior. report that anxiety- depressive-like behaviors are resistant BLS as well both conventional new antidepressants, ketamine. Remarkably, unveil potentiates effect this mediated via rod retinal photoreceptors. Furthermore, demonstrate chemogenetic activation lateral habenula (LHb) astroglia serotonin (5-HT) depletion prevent potentiating on despair. These results reveal, first time, enhances efficacy antidepressants an unexpectedly circuit involving rods, LHb 5-HT.

Language: Английский

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Effects of blue light during and after exposure on auditory working memory

Journal of PHYSIOLOGICAL ANTHROPOLOGY, Journal Year: 2025, Volume and Issue: 44(1)

Published: May 22, 2025

Abstract Introduction Exposure to short-wavelength light (i.e., blue light) has been shown enhance cognitive function in humans. While most prior studies have focused on visuospatial working memory, the effects of auditory particularly tasks involving phonological loop, remain underexplored. This study investigated both during- and post-exposure memory performance. Methods Fifteen healthy university students (13 males, 2 females; 21.47 ± 1.06 years old) participated a randomized crossover design. Each participant was exposed three lighting conditions for approximately 20-min: (λ max = 476 nm, illuminance 21.84 lx, 13.8 log photons/s-1.cm-2, melanopic EDI 169.68 lx), amber 580 61.65 13.5 2.87 lx) dim (baseline; < 5.00 lx). session separated by one-week washout period. To mitigate order effects, sequence across participants. The modified version Sternberg task performed during exposure after 10-min break During- vs Post-exposure phase). accuracy, reaction time, subject anxiety sleepiness were measured. Results In phase, significantly improved accuracy compared ( p 0.01, d 0.66) 0.67). No significant differences observed or time conditions. Anxiety levels higher (vs. amber: 0.013, 0.96; vs. dim: 0.027, 0.83), while remained unchanged. Conclusions Blue may with delayed effect, independent vigilance processing speed. these findings are promising, preliminary require validation larger more diverse populations.

Language: Английский

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Turn off that night light! Light-at-night as a stressor for adolescents

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 31, 2024

Light-at-night is known to produce a wide variety of behavioral outcomes including promoting anxiety, depression, hyperactivity, abnormal sociability, and learning memory deficits. Unfortunately, we all live in 24-h society where people are exposed light-at-night or light pollution through night-shift work - the need for all-hours emergency services as well building street-lights, making exposure practically unavoidable. Additionally, increase screentime (tvs smart devices) during night also contributes poorer sleep impairments. Compounding these factors fact that adolescents tend be "night owls" prefer an evening chronotype compared younger children adults, so teenagers will have higher likelihood being light-at-night. Making matters worse prevalence high-school start times 8 am earlier combination too early school times, night, preference chronotypes recipe reduced sleep, which can contribute increased susceptibility issues this population. As such, mini-review show, using both human rodent model studies, how affects stress responses, connecting photic signaling circadian timing system hypothalamic-pituitary adrenal axis. review demonstrate more likely exhibit behavior response due changes development hormone regulation time period, discuss potential interventions help mitigate negative effects.

Language: Английский

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Brainwave Patterns and Metabolic Adaptations in Rowers Crossing the Atlantic: A Case Series Pilot Study

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Introduction: This pilot study was designed to test the hypothesis that quantitative electroencephalographic (qEEG) measurements reflect physiological adaptations for brain energy reallocation. The focused on a team of three well-matched male rowers participating in 30-day, 2,650-mile continuous transatlantic rowing competition, examining effects extreme, prolonged stress function and metabolic adaptations. Methods: Measurements at start finish lines included body weight, height, waist circumference, fat, panel hormones biochemical markers. Post-race qEEG parameters were recorded under eyes-open (EO) eyes-closed (EC) conditions. data compared reference population (ages 6-90 years) an age-matched 27-year-old medical student serving as control subject. analysis evaluated voltage amplitudes, wave distribution patterns, theta-to-beta ratios (TBR), coherence levels. Hormonal changes oxidative markers also assessed before after race. Results: Two exhibited post-race dominance high-frequency beta activity, while one displayed co-dominance delta waves. Compared subject (TBR = 1.25), rowers' low TBRs (< 0.2) indicated high vigilance relaxation during EC Cortisol levels increased all associated with >1 SD above mean. Testosterone decreased two but one; smallest cortisol increase corresponded largest testosterone decrement. Decreases correlated shift from right- left-sided alpha asymmetry, consistent redistribution nondominant hemisphere. pattern observed Increased rower linked decrease percentage sites exhibiting normal theta frequencies, indicating potential role Conclusion: findings suggest response extreme stress, supporting is reallocated optimize performance. correlations between hormonal changes, markers, provide preliminary evidence mechanisms These insights highlight identify biomarkers adaptation lay groundwork larger studies further elucidate these mechanisms.

Language: Английский

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Light-eye-body axis: exploring the network from retinal illumination to systemic regulation

Theranostics, Journal Year: 2024, Volume and Issue: 15(4), P. 1496 - 1523

Published: Dec. 31, 2024

The human body is an intricate system, where diverse and complex signaling among different organs sustains physiological activities. eye, as a primary organ for information acquisition, not only plays crucial role in visual perception but also, increasing evidence suggests, exerts broad influence on the entire through circuits upon receiving light signals which called non-image-forming vision. However, extent mechanisms of light's impact eyes remain insufficiently explored. There also dearth comprehensive reviews elucidating interplay between light, systemic connections to body. Herein, we propose concept light-eye-body axis systematically encapsulate extensive effects received by retina We reviewed visual-neural structure basis axis, summarized mechanism regulate whole current research status challenges within pathological processes involved axis. Future should aim expand explore its deeper mechanisms. Understanding investigating will contribute improving lighting conditions optimize health guide establishment phototherapy standards clinical practice.

Language: Английский

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