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

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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.

Язык: Английский

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The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross‐Sectional Studies

Annals of Neurology, Год журнала: 2023, Номер 94(4), С. 672 - 683

Опубликована: Июнь 28, 2023

Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, clinical this remains lacking.In study, index for diffusion tensor image analysis along perivascular space (ALPS index) was calculated to evaluate function.Overall, 289 patients with PD were enrolled in cross-sectional study. The ALPS found be negatively correlated age, severity, dyskinesia. In longitudinal information on a total 95 5-year follow-up examinations collected from Progression Marker Initiative, 33 which classified into low group, all others mid-high group based first tertile baseline index. results regression indicated significant main effect autonomic dysfunction, as well activities daily living. addition, had faster deterioration MDS-UPDRS part III II, Symbol Digit Modalities Test Hopkins Verbal Learning Test. Path showed acted mediator tTau/ Aβ1-42 cognitive change score at year 4 5.The index, neuroimaging marker function, motor symptoms, predictive symptoms function. Additionally, function may mediate role toxic protein decline. ANN NEUROL 2023;94:672-683.

Язык: Английский

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Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration

Cells, Год журнала: 2024, Номер 13(3), С. 286 - 286

Опубликована: Фев. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Язык: Английский

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Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage

Brain Research Bulletin, Год журнала: 2024, Номер 216, С. 111045 - 111045

Опубликована: Авг. 5, 2024

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution acute phase ICH, though precise mechanisms remain unclear. Recent findings have highlighted glymphatic system (GS) as a crucial component intracranial cerebrospinal fluid circulation, playing significant role clearance post-ICH. This study investigates link between SIM efficacy GS. Our experimental results show alleviates GS damage ICH-induced rats, resulting improved outcomes such reduced brain edema, neuronal apoptosis, degeneration. Further analysis reveals SIM's effects are mediated through VEGF-C/VEGFR3/PI3K-Akt pathway. advances our understanding mechanism promoting underscores potential targeting for ICH treatment.

Язык: Английский

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

Neurobiology of Disease, Год журнала: 2025, Номер 205, С. 106791 - 106791

Опубликована: Янв. 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.

Язык: Английский

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Diffusion along Perivascular Spaces as a Marker for Glymphatic System Impairment in Huntington's Disease

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Abstract Background The aim was to investigate if glymphatic function is impaired in patients with Huntington's disease (HD) and its clinical relevance. Methods Forty‐nine subjects carrying mutant Huntingtin (m HTT ), comprising 35 manifest (mHD) 14 pre‐manifest (PreHD), healthy controls (HC) were recruited this study. diffusion along perivascular spaces (ALPS) index the percentage of space basal ganglia (pPVS_BG) obtained different groups. discrimination effects ALPS detected using receiver operating characteristic (ROC) analysis, correlations features HD further analyzed. Results decreased m carriers compared HCs, it lower mHD PreHD patients. ROC analysis showed that could discriminate from HC (AUC [area under curve] = 0.903), 0.886), 0.755). Lower correlated greater burden, severity disease, lager pPVS_BG, brain volume thickness cortices. Regression predict performance motor cognitive functions. Mediation revealed partially mediated CAG repeat age on decline HD. Conclusions This study demonstrated impairment system, especially paraventricular white matter BG, manifestations, structural changes carriers. © 2025 Author(s). Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Язык: Английский

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Aquaporin-4 and Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1672 - 1672

Опубликована: Янв. 30, 2024

The water-selective channel aquaporin-4 (AQP4) is implicated in water homeostasis and the functioning of glymphatic system, which eliminates various metabolites from brain tissue, including amyloidogenic proteins. Misfolding α-synuclein protein its post-translational modifications play a crucial role development Parkinson’s disease (PD) other synucleopathies, leading to formation cytotoxic oligomers aggregates that cause neurodegeneration. Human animal studies have shown an interconnection between AQP4 dysfunction accumulation; however, specific these mechanisms remains unclear. This review summarizes current knowledge on progression pathology, considering possible effects dysregulation molecular can impact modification, accumulation aggregation. It also highlights future directions help study protective during PD neurodegenerative diseases.

Язык: Английский

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Ginkgolide B can alleviate spinal cord glymphatic system dysfunction and provide neuroprotection in painful diabetic neuropathy rats by inhibiting matrix metalloproteinase-9

Neuropharmacology, Год журнала: 2024, Номер 250, С. 109907 - 109907

Опубликована: Март 14, 2024

Язык: Английский

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Association between glymphatic system function and cognitive impairment in elderly patients with late-onset epilepsy

Epilepsy & Behavior, Год журнала: 2025, Номер 164, С. 110258 - 110258

Опубликована: Янв. 18, 2025

Язык: Английский

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Resveratrol differentially affects MMP‐9 release from neurons and glia; implications for therapeutic efficacy

Journal of Neurochemistry, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Abstract Resveratrol, a naturally occurring polyphenol that activates sirtuin 1 (SIRT1), has been shown to reduce overall levels of matrix metalloprotease‐9 (MMP‐9) in cerebrospinal fluid (CSF) samples from patients with Alzheimer's dementia (AD). Depending on the site release, however, MMP‐9 potential improve or impair cognition. In particular, its release microglia pericytes proximal blood brain barrier can damage basement membrane, while neuronal activity‐dependent this protease glutamatergic neurons instead promote dendritic spine expansion and long‐term potentiation synaptic plasticity. present study, we test hypothesis resveratrol reduces CSF APOE4, an allele associated increased glial inflammation. We also examine possibility inflammation‐associated MMP cultured glia but spares cortical neurons. observe decreases MMP‐2 AD patients. Resveratrol tissue inhibitor metalloproteinases‐1 (TIMP‐1), glial‐derived protein restricts transmission, individuals homozygous for APOE4. Consistent these results, basal lipopolysaccharide (LPS)‐stimulated TIMP‐1 astrocytes. contrast, does not inhibit Overall, results are consistent potentially maladaptive activated glia, neuroplasticity‐promoting is spared. neurocan brevican, extracellular components restrict neuroplasticity, both glia. These data underscore diversity resveratrol's actions respect affected cell types molecular targets suggest further studies may be warranted determine if effects could make it useful adjunct AD‐ and/or anti‐amyloid therapy‐related barrier.

Язык: Английский

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