New perspectives on the glymphatic system and the relationship between glymphatic system and neurodegenerative diseases

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: 205, P. 106791 - 106791

Published: Jan. 6, 2025

Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial (ISF), facilitates movement metabolic substances within brain, serving functions akin to those peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on removal pathological in ND. article elucidates recent discoveries regarding system updates relevant concepts model. It discusses potential roles ND, including Alzheimer's disease (AD), Parkinson's (PD), multiple atrophy (MSA), proposes as therapeutic target for these conditions.

Language: Английский

---

Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms treatments remain elusive. Here we report therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model disease. Our findings reveal that treatment prevents memory decline 4-month-old mice motivation loss 14-month-old mice, accompanied restoration glial water channel aquaporin-4 polarity, improved brain drainage efficiency, reduction hippocampal lipid accumulation. We further demonstrate beneficial effects are mediated through activation vLGN/IGL-Re visual circuit. Notably, concomitant use anti-Aβ antibody with demonstrates soluble Aβ clearance performance mice. These offer functional evidence on Aβ-related pathologies suggest its as supplementary strategy to augment efficacy antibody-based therapy. Treatments for (AD) limited. Here, authors show activates circuit boost glymphatic drainage, enhances memory, motivation, therapy AD.

Language: Английский

---

Impact of Glucocorticoid‐Associated Stress‐Like Conditions on Aquaporin‐4 in Cultured Astrocytes and Its Modulation by Adenosine A_2A Receptors

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(1)

Published: Jan. 1, 2025

ABSTRACT Astrocytes participate in brain clearance of extracellular proteins and metabolites, through the activity water channel aquaporin‐4 (AQP4), which can be deregulated stress‐related disorders, impairing waste clearance. The present study investigates impact dexamethasone (Dexa), a synthetic glucocorticoid used as simplified vitro stress model, on astrocytic AQP4 its modulation by adenosine A 2A receptors (A R), blockade reverses conditions related with maladaptive stress, such anxiety depression. primary cultures, assessed using 5 kDa FITC‐dextran 45 TRITC‐dextran uptake, was decreased 24 h exposure to 100 nM Dexa. Dexa α‐syntrophin density, protein‐targeting processes, potentially affecting location and, consequently, activity. Accordingly, influx (assessed calcein fluorescence), paralleled impairment dextran Dexa‐induced decrease protein uptake prevented activator TGN‐073 R antagonism SCH58261, showing that AQP4‐mediated controlled this Dexa‐simplified model. Additionally, effects were confirming modulate function. This conclusion reinforced observed AQP4/A physical interaction astrocytes. Overall, data indicate affect localisation role modulated R. These findings unveil novel therapeutic mechanism prevent accumulation associated neurological disorders tinkering image

Language: Английский

---

Longitudinal Effects of Lifetime Caffeine Consumption on Levels of Depression, Anxiety, and Stress: A Comprehensive Review

Current Nutrition Reports, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 1, 2025

Abstract Purpose of Review Caffeine has high bioavailability and a purine-like alkaloid structure. It exerts wide-ranging physiological effects by binding to adenosine receptors throughout the human body. Through activation those receptors, it can regulate many events in The impact caffeine consumption on depression, anxiety, stress, health remains unclear, constituting an important knowledge gap. This review was conducted examine stress levels offer some recommendations for its future use. Recent Findings We performed comprehensive literature search using PubMed, Web Science Google Scholar databases original articles published recent years “caffeine metabolism”, mechanism”, “anxiety”, “depression”, “stress”. Caffeine, which antagonistic effect adenosine, reduce risk symptoms depression improve general mental modulating central nervous system neurotransmitter systems. However, increases anxiety levels, are often seen together with observed due high-dose consumption. Summary Caffeine’s may vary depending different factors, but level is particularly attention should be paid upper limits reference values while evaluating amounts.

Language: Английский

---

Relationships Between Glymphatic System Activity and Tau Burden, Dopaminergic Impairment, Abnormal Glucose Metabolism in Progressive Supranuclear Palsy

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by dopaminergic impairment and abnormal glucose metabolism. The glymphatic system can promote the elimination of tau protein. association between function pathological hallmark in neuroimaging remains unknown. Methods Diffusion tensor imaging (DTI) positron emission tomography (PET) scanning with 18 F‐Florzolotau, F‐FPCIT, F‐FDG were performed PSP patients. DTI analysis along perivascular space (ALPS) index was computed to assess function, while semi‐quantitative value employed measure burden impairment. PSP‐related pattern (PSPRP) served as an indicator metabolic brain network activity. Results patients exhibited changes ALPS deposition. index, deposition, PSPRP expression showed significant correlations clinical scores. Additionally, correlated deposition expression. However, neither nor scores striatum dysfunction. Finally, subcortical regions mediating effects Conclusion dysfunction associated activity independent PSP.

Language: Английский

---

Innovations in noninvasive sensory stimulation treatments to combat Alzheimer’s disease

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(2), P. e3003046 - e3003046

Published: Feb. 28, 2025

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide. There no known cure for AD, highlighting an urgent need new, innovative treatments. Recent studies have shed light on promising, noninvasive approach using sensory stimulation as potential therapy AD. Exposing patients to and sound pulses at frequency of 40 hertz induces brain rhythms in the gamma range that are important healthy activity. Using this treatment animal models, we now beginning understand molecular, cellular, circuit-level changes underlie improvements pathology, cognition, behavior. A mechanistic understanding basic biology underlies 40-hertz will inform ongoing clinical trials offer promising avenue without side effects high costs typically associated with pharmacological interventions. Concurrent advancements neurotechnology can also noninvasively stimulate illuminating new possibilities alternative therapies. Altogether, these approaches could herald era treating making them beacon hope patients, families, caregivers facing challenges debilitating condition.

Language: Английский

---

Widespread and Prolonged Pain May Reduce Brain Clearance Capacity Only via Sleep Impairment: Evidence from Participants with Knee Pain

Journal of Pain, Journal Year: 2025, Volume and Issue: unknown, P. 105356 - 105356

Published: March 1, 2025

Language: Английский

---

Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: 4

Published: March 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Language: Английский

---

Terahertz Photoneuromodulation of Lateral Orbitofrontal Cortex Neurons Ameliorates Stress-induced Depression and Cognitive Impairment

Fundamental Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Depression imposes a staggering global socioeconomic burden. Current pharmacotherapies face major limitations, including slow efficacy, adverse effects, and non-response rates of up to 55%, necessitating novel therapeutic modalities. This study introduces terahertz (THz) photoneuromodulation as an innovative physical intervention for depression, offering several advantages over conventional pharmacological or optogenetic approaches. Mild THz circumvents the need exogenous agents genetic modifications, mitigating potential risks while precisely modulating neurotransmitter levels neuronal excitability alleviate depression-like behaviors. In chronic restraint stress (CRS) mouse model, photostimulation rapidly attenuated hyperactivity increased serotonin by 107.5% ± 45.3% in lateral orbitofrontal cortex glutamatergic neurons (OFCGlu) compared those treated with antidepressants. led marked improvements depressive-like behaviors cognitive function. Furthermore, modulation OFC activity recapitulated effects chemogenetic inhibition, underscoring OFC's pivotal role regulating depressive states. research unveils promising, safe, rapid-acting, durable neurotherapeutic strategy addressing persistent unmet needs depression treatment.

Language: Английский

---

Forty‐hertz sensory entrainment impedes kindling epileptogenesis and reduces amyloid pathology in an Alzheimer disease mouse model

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

Published: Dec. 30, 2024

The 5xFAD mouse model of Alzheimer disease (AD) recapitulates amyloid-beta (Aβ) deposition and pronounced seizure susceptibility observed in patients with AD. Forty-hertz audiovisual stimulation is a noninvasive technique that entrains gamma neural oscillations can reduce Aβ pathology modulate glial expression AD models. We hypothesized 40-Hz sensory would improve mice this be associated reduction plaques modulation phenotypes.

Language: Английский

---