High-intensity interval training ameliorates Alzheimer's disease-like pathology by regulating astrocyte phenotype-associated AQP4 polarization

Theranostics, Год журнала: 2023, Номер 13(10), С. 3434 - 3450

Опубликована: Янв. 1, 2023

Background: Alzheimer's disease (AD), one of the most common forms dementia, is a widely studied neurodegenerative characterized by Aβ accumulation and tau hyperphosphorylation. Currently, there no effective cure available for AD.The astrocyte AQP4 polarized distribution-mediated glymphatic system essential abnormal clearance potential therapeutic target AD.However, role exercise on distribution association between phenotype polarization are poorly understood.Methods: Using streptozotocin (STZ)-induced sporadic AD rat model, we investigated effects high-intensity interval training pathologies.The Branes maze task was conducted to measure spatial learning memory.Immunofluorescence staining NeuN with TUNEL, Fluoro-Jade C, relative neuronal damage markers applied apoptosis, neurodegeneration, damage.Sholl analysis carried out analyze morphology microglia.Line-scan analysis, 3D rendering, orthogonal view were colocalization.Western blot enzyme-linked immunosorbent assay (ELISA) examine Aβ, respectively.An APP/PS1 transgenic mice model used confirm key findings.Results: High-intensity (HIIT) alleviates cognitive dysfunction in STZ-induced AD-like models provides neuroprotection against damage, loss.Additionally, HIIT improved drainage from cortex hippocampus via kidney.Further mechanistic studies support that beneficial might be due, part, glial cells neurotoxic towards neuroprotective phenotype.Furthermore, an intriguing finding our study strongly correlated phenotype.We found A2 exhibited more evident than A1 phenotype. Conclusion:Our findings indicate ameliorates disease-like pathology regulating phenotype-associated polarization.These changes promote p-tau brain tissue through kidney.

Язык: Английский

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Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Май 12, 2023

Abstract Neurological conditions, including cognitive impairment and Alzheimer’s disease (AD), impose a huge burden on society, affecting millions of people globally. In addition to genetic factors, recent studies indicate that environmental experiential factors may contribute the pathogenesis these diseases. Early life adversity (ELA) has profound impact brain function health later in life. rodent models, exposure ELA results specific deficits aggravated AD pathology. Extensive concerns have been raised regarding higher risk developing impairments with history ELA. this review, we scrutinize findings from human animal focusing connection AD. These discoveries suggest ELA, especially at early postnatal stages, increases susceptibility terms mechanisms, could lead dysregulation hypothalamus-pituitary-adrenal axis, altered gut microbiome, persistent inflammation, oligodendrocyte dysfunction, hypomyelination, aberrant adult hippocampal neurogenesis. Crosstalks among events synergistically Additionally, discuss several interventions alleviate adverse consequences Further investigation into crucial area will help improve management reduce related neurological conditions.

Язык: Английский

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Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances

Aging and Disease, Год журнала: 2023, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2023

Alzheimer’s disease, one of the most common forms dementia, is characterized by a slow progression cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered various side effects limited efficacy. Despite considerable research, practical have not been developed. Increasing evidence shows that glial cells, especially microglia astrocytes, essential in initiation AD. During progression, activated resident increases ability resting astrocytes to transform into reactive promoting neurodegeneration. Extensive clinical molecular studies show involvement astrocyte-mediated neuroinflammation pathology, indicating may be potential therapeutic targets This review will summarize significant recent advances pathogenesis three parts. First, we typical pathological changes discuss terms function phenotypic changes. Second, describe astrocytes’ physiological role These roles include inflammatory response, “eat me” “don’t eat signals, Aβ seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, demyelination. Last, pharmacological non-pharmacological therapies targeting We conclude development Therefore, understanding new critical future trials. Moreover, pharmacological, with specific investigating damage repair, promising research direction regarding treatment prevention.

Язык: Английский

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Oligodendrocyte progenitor cells in Alzheimer’s disease: from physiology to pathology

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Ноя. 14, 2023

Abstract Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring contributing to the integrity of blood–brain barrier (BBB). However, under pathological circumstances Alzheimer’s disease (AD), brain’s microenvironment undergoes detrimental changes that significantly impact OPCs their functions. Starting OPC functions, we delve into transformation myelin-producing oligodendrocytes, intricate signaling interactions other central nervous system (CNS), fascinating process which influences function affects CNS homeostasis. Moreover, discuss essential role BBB highlight critical contribution forming CNS-protective barriers. In context AD, deterioration local brain is discussed, mainly focusing on neuroinflammation, oxidative stress, accumulation toxic proteins. The disturb delicate balance brain, impacting regenerative capacity compromising integrity. Under conditions, experience significant alterations migration proliferation, leading impaired differentiation a reduced ability produce mature oligodendrocytes. degeneration become increasingly active progressive neurodegeneration. Finally, summarize current therapeutic approaches targeting AD. Strategies revitalize senescence, modulate pathways enhance differentiation, explore potential avenues are promising alleviating AD function. conclusion, this review highlights indispensable involvement pathogenesis interplay between underscores complexity neurodegenerative diseases. Insights from studying conditions provide foundation for innovative strategies fostering Future research will advance our understanding management diseases, ultimately offering hope effective treatments improved quality life those affected by related disorders.

Язык: Английский

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Remote photobiomodulation ameliorates behavioral and neuropathological outcomes in a rat model of repeated closed head injury

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 11, 2025

Repeated closed-head injuries (rCHI) from activities like contact sports, falls, military combat, and traffic accidents pose a serious risk due to their cumulative impact on the brain. Often, rCHI is not diagnosed until symptoms of irreversible brain damage appear, highlighting need for preventive measures. This study assessed prophylactic efficacy remote photobiomodulation (PBM) targeted at lungs against rCHI-induced injury associated behavioral deficits. Utilizing "Marmarou" weight-drop model, was induced in rats days 0, 5, 10. Remote PBM, employing an 808 nm continuous wave laser, administered daily 2-min sessions per lung side over 20 days. Behavioral deficits were through three-chamber social interaction, forced swim, grip strength, open field, elevated plus maze, Barnes maze tests. Immunofluorescence staining 3D reconstruction evaluated neuronal damage, apoptosis, degeneration, morphology microglia astrocytes, as well astrocyte microglia-mediated excessive synapse elimination. Additionally, 16S rDNA amplicon sequencing analyzed changes microbiome following PBM treatment. Results demonstrated that significantly improved depressive-like behaviors, motor dysfunction, interaction impairment while enhancing strength reducing degeneration by rCHI. Analysis revealed enrichment lipopolysaccharide (LPS) biosynthesis pathways, suggesting potential link neuroprotection. Furthermore, mitigated hyperactivation cortical astrocytes reduced synaptic phagocytosis these cells, its strategy with neuroprotective effects.

Язык: Английский

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Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model

Brain Research Bulletin, Год журнала: 2025, Номер 223, С. 111280 - 111280

Опубликована: Фев. 25, 2025

The impairment of cognitive function has been associated with Alzheimer's disease (AD). Exercise exerts a positive modulatory effect on cognition by reducing synapse injury. However, limited in vivo evidence is available to validate the neuroprotective TREM2 synaptic this phenomenon. Here, we aim explore whether physical exercise pretreatment alters Aβ-induced recognition memory structural plasticity within hippocampus AD rats. METHODS：: In study 1, fifty-two Sprague-Dawley (SD) rats were randomly divided into following four groups: control group (C group, n = 13), (AD 4 weeks and (Exe+AD blank (Exercise 13). Four treadmill intervention was performed, model established intra-cerebroventricular injection (ICV) Aβ1-42 protein. After 3 weeks, also conducted novel object test evaluate behavior assessment. Golgi staining transmission electron microscopy used morphology ultrastructure neurons. Western blotting measure expression hippocampal proteins. Extracellular neurotransmitters detected microdialysis coupled high-performance liquid chromatography. 2, 33 SD three 11), AAV-Control (AAV-Control+Exe+AD AAV-TREM2 (AAV-TREM2 +Exe+AD 11). Stereotactic intracerebral bilateral performed achieve microglial down-expression using adeno-associated virus (AAV) CD68 promoter. Aβ injection, all received molecular experiment, which same experiment 2. Novel index significantly decreased, western blot demonstrate that protein decreased (P < 0.001). But reversed phenomenon(P addition, compared Con neuron from Exe+AD exhibited more complex branching pattern 0.05). And impaired observed group. Hippocampal synaptic-related (SYX, SYP, GAP43, PSD95) neurotransmitter (DA, Glu, GABA) 0.01) neuroprotection can be found are inhibition injury activate when blockade reduced brain protective rat model, including increased damage neuronal dendritic complexity, ultrastructure, decrease synapses-related protein, typical neurotransmitter. Treadmill facilitated acquisition via TREM2-mediated an model.

Язык: Английский

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Targeting Alzheimer’s Disease: The Critical Crosstalk between the Liver and Brain

Nutrients, Год журнала: 2022, Номер 14(20), С. 4298 - 4298

Опубликована: Окт. 14, 2022

Alzheimer’s disease (AD), an age-related neurodegenerative disorder, is currently incurable. Imbalanced amyloid-beta (Aβ) generation and clearance are thought to play a pivotal role in the pathogenesis of AD. Historically, strategies targeting Aβ have typically focused on central clearance, but with limited clinical success. Recently, contribution peripheral systems, particularly liver, has sparked increased interest. In addition, AD presents pathological features similar those metabolic syndrome, critical involvement brain energy disturbances this been recognized. More importantly, liver may be key regulator these abnormalities, far beyond our past understanding. Here, we review recent animal findings indicating that dysfunction represents early event pathophysiology. We further propose compromised by aberrant hepatic physiological processes contribute neurodegeneration. The synthesis product, fibroblast growth factor 21 (FGF21), management also discussed. A deeper understanding communication between lead new opportunities for diagnosis treatment

Язык: Английский

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Sexual dimorphism in the peripheral metabolic homeostasis and behavior in the TgF344‐AD rat model of Alzheimer's disease

Aging Cell, Год журнала: 2023, Номер 22(7)

Опубликована: Апрель 24, 2023

Alzheimer's disease (AD), a prevalent form of dementia, is characterized by the decline cognitive abilities with age. Available treatment options for AD are limited, making it significant public health concern. Recent research suggests that metabolic dysfunction plays role in development AD. In addition, insulin therapy has been shown to improve memory patients decline. this study, we report first examination body composition, peripheral sensitivity, and glucose tolerance relation behavioral assessments learning, memory, anxiety TgF344-AD rat model Results from tests show female rats exhibit impaired clearance reduced sensitivity at both 9 12 months age, while males display no differences even improved months. Morris Water Maze assessment learning reveal male impairments only Furthermore, results open field elevated plus maze suggest increased age; however, were detected or Overall, our findings metabolism, commonly associated type 2 diabetes, occur before simultaneously sexually dimorphic manner model.

Язык: Английский

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Myelin Pathology in Alzheimer's Disease: Potential Therapeutic Opportunities

Aging and Disease, Год журнала: 2023, Номер 15(2), С. 698 - 698

Опубликована: Авг. 2, 2023

Cellular senescence is an irreversible and multifaceted process inducing tissue dysfunction organismal aging, thus the clearance of senescent cells can prevent or delay onset aging-related pathologies. Herein, we developed augmented photothermal therapy strategy integrated with antibody against β2-microglobulin (aB2MG) immune adjuvant imiquimod (R837) to effectively accelerate cell apoptosis under a near-infrared light. With this strategy, designed CroR@aB2MG enables targeting application concomitantly, initiation subsequently, finally realization protective effects senescence. Our results showed that photo-induced heating effect caused quickly undergo synchronous response accelerated in vitro vivo. Therefore, photoactivated speedy clearing may provide efficient way for treatment senescence-related diseases by eliminating biomaterials.

Язык: Английский

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Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis

Journal of Alzheimer s Disease, Год журнала: 2024, Номер 98(3), С. 825 - 835

Опубликована: Март 8, 2024

Background: The Food and Drug Administration (FDA) has approved lecanemab aducanumab is reviewing donanemab, but they have questionable efficacy, serious side effects are costly, whereas melatonin administration aerobic exercise for a short time may overcome these problems. Objective: We aim to compare the efficacy on cognitive function, tolerability acceptability of with lecanemab, in people mild AD MCI. Methods: systematically reviewed relevant randomized placebo-controlled trials (RCTs) PubMed, Cochrane Library, CINHAL, ClinicalTrials.gov performed network meta-analyses. Results: analysis included 10 4,599 patients. Although were significantly more effective than placebo primary analysis, there was significant heterogeneity. In sensitivity excluding exercise, placebo, no Aerobic less acceptable placebo. Donanemab, tolerable donanemab CONCLUSIONS: Melatonin be better potential disease-modifying treatment decline might also if continued, as it well tolerated effective, although valid due Another limitation small number participants.

Язык: Английский

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