Behaviour Hallmarks in Alzheimer’s Disease 5xFAD Mouse Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6766 - 6766

Published: June 20, 2024

The 5xFAD transgenic mouse model widely used in Alzheimer’s disease (AD) research recapitulates many AD-related phenotypes with a relatively early onset and aggressive age-dependent progression. Besides developing amyloid peptide deposits alongside neuroinflammation by the age of 2 months, as well exhibiting neuronal decline 4 months that intensifies 9 these mice manifest broad spectrum behavioural impairments. In this review, we present extensive repertoire dysfunctions mice, organised into four categories: motor skills, sensory function, learning memory abilities, neuropsychiatric-like symptoms. problems, associated agility reflex movements, balance coordination, skeletal muscle typically arise time reach age. function (such taste, smell, hearing, vision) starts to deteriorate when buildups spread related anatomical structures. cognitive functions, encompassing such visual recognition, associative, spatial working, reference learning, show signs from 6 Concerning symptoms, comprising apathy, anxiety depression, willingness for exploratory behaviour, it is believed motivational changes emerge approximately Unfortunately, numerous studies different laboratories are often contradictory on conclusions drawn identification age, making preclinical rodent models not easily translatable humans. This variability likely due range factors animals themselves, housing husbandry conditions, experimental settings. forthcoming studies, greater clarity details conducting testing could minimise inconsistencies ensure reliability reproducibility results.

Language: Английский

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Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the Brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD Mice

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 17, 2025

Abstract Background Alzheimer’s disease (AD) is a devastating neurodegenerative and has no treatment that can cure or halt the progression. This study explored therapeutic potential of lithium salt dissolved in Ryanodex formulation vehicle (RFV) delivered to brain by intranasal application. We first compared concentrations blood wild-type mice following oral administration chloride (LiCl) either RFV water. The beneficial side effects versus LiCl these were assessed mechanisms underlying efficacy anti-inflammation anti-pyroptosis brains also investigated both 5XFAD Disease brains. Methods For concentrations, (WT) B6SJLF1/J at 2 months age treated with (3 mmol/kg) Brain measured various times after drugs administration. Brain/blood concentration ratios then determined. studying their mechanisms, WT daily, Monday Friday each week, beginning 9 12-week duration. Animal behaviors for depression (tail suspension), cognition (fear conditioning Y maze), olfaction (buried food test), motor functions (rotarod) 5 12 months. Blood tissue harvested from 13 biomarkers thyroid (thyroid stimulating hormone, TSH) kidney (creatinine) using ELISA. Changes protein expression levels endoplasmic reticulum Ca 2+ release channels type 1 InsP 3 receptors (InsP R-1), malondialdehyde (MDA)-modified proteins 4-hydroxy-2-nonenal (4-HNE), pyroptosis regulatory (NLR family pyrin domain containing (NLRP3), cleaved caspase-1, N-terminal Gasdermin D (GSDMD)), cytotoxic (IL-1β, IL-18, IL-6, TNF-α) cytoprotective (IL-10) cytokines synapse (PSD-95, synapsin-1) determined immunoblotting. Mouse body weights monitored regularly. Results Compared nanoparticles, markedly decreased time range 30–120 min. ratio brain/blood significantly increased, comparison those Intranasal inhibited memory loss depressive behavior adult aged mice. Additionally effectively suppressed increases R-1, intracellular oxidative stress markers (4-HNE-bound MDA-modified proteins), activation (NLRP3, GSDMD) TNF-α), but reversed down-regulation cytokine IL-10. alleviated postsynaptic PSD-95, not synapsin-1, level function marker creatinine was increased than an age-dependent manner this elevation abolished delivery RFV. weeks did affect function, nor it smell muscle weight. Conclusion ratio, its robustly protected against depressive-like behavior, while had concerning toxicity These lithium-induced strongly associated lithium’s suppression R-1 channel receptor increase, pathological neuroinflammation pathway, as well synaptic PSD-95. could become effective potent inhibitor inflammation/pyroptosis CNS serve new AD-associated dementia minimal unwanted including peripheral organ toxicity. Graphical Formulation Vehicle cognitive dysfunction depression-like mice, on functions. I InsP3 (InsP3R-1) Ca2+ proteins, stress, pathway (Increased NLRP3, GSDMD, IL-1β IL-18). drug treating AD.

Language: Английский

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The synergistic extract of Zophobas atratus and Tenebrio molitor regulates neuroplasticity and oxidative stress in a scopolamine-induced cognitive impairment model

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: April 23, 2025

Neurodegenerative disorders, such as Alzheimer's disease, arise from neuroinflammation, which leads to cognitive and memory impairment. Scopolamine is commonly used induce deficits in mouse models. This study investigated the neuroprotective potential of a Zophobas atratus (Za) Tenebrio molitor (Tm) extract mixture (ZaTm mixture) mitigating scopolamine-induced mice. Behavioral assessments, including Morris water maze, Y-maze, light/dark tests, demonstrated that ZaTm significantly enhanced function treated Furthermore, restored disrupted expression choline acetyltransferase acetylcholinesterase hippocampi scopolamine-treated Additionally, glutamatergic/GABAergic dysfunction was markedly improved following treatment with mixture. The also exhibited effects by enhancing activity antioxidants, glutathione malondialdehyde, key enzymes, catalase superoxide dismutase. Moreover, it effectively inhibited senescence hippocampus modulating AMPK/SIRT BDNF-Akt/mTOR signaling pathways. highlights promising novel therapeutic agent functional food for prevention disease other neurodegenerative disorders.

Language: Английский

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The neural basis of neuropsychiatric symptoms in Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Dec. 5, 2024

Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy and aggression affect up to 90% of Alzheimer's disease (AD) patients. These significantly increase caregiver stress institutionalization rates, more importantly they are correlated with faster cognitive decline. However, the neuronal basis NPS in AD remains largely unknown. Here, we review current understanding related pathology studies patients mouse models. Clinical indicate that prevalence severity vary across different stages types. Neuroimaging postmortem have suggested pathological changes anterior cingulate cortex, hippocampus, prefrontal amygdala linked NPS, although precise mechanisms remain unclear. Studies models indicated amyloid-beta tau-related neurodegeneration cortex NPS-like behavioral deficits. A better phenotypes will pave way for developing a management strategy

Language: Английский

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