Chuangxiong-Danggui Herb Pair Alleviated Cognitive Deficits of App/Ps1 Mice by Promoting Fundc1-Mediated Mitophagy

Published: Jan. 1, 2025

Background: Disruption of receptor-mediated mitophagy contributes to neuronal damage in AD. Chuangxiong-Danggui herb pair (CDHP) is classic herbal applied treating neurodegenerative diseases like AD, ALS, PD. Studies have indicated the neuroprotective effects CDHP, underlying mechanisms by which CDHP attenuates impairment AD remains be elucidated.PurposeThe objective this work was investigate anti-AD mechanism APP/PS1 mice mainly based on FUNDC1-mediated mitophagy.MethodsBehavioral assessments were conducted C57BL/6J and following treatment, alongside an evaluation morphology hippocampal region. In vitro, HT-22 cells induced Aβ25-35 before treated with CDHP. The investigated using transmission electron microscopy, Golgi staining, immunofluorescence, siRNA, Western blot analysis.ResultsResults from passive avoidance test MWM that significantly mitigated cognitive deficits mice, accompanied a reduction pathological CA1 CA3 regions hippocampus. Further testing found significant dendritic spines density rescued protein synaptophysin PSD-95 elevated group, while Aβ plaques deposition reduced. Simultaneously, markedly inhibits apoptosis decreased levels Cleaved Caspase-12 enhanced expression Bcl-2/Bax both vivo vitro. Additionally, improved mitochondrial function model decreasing abnormal mitochondria increasing COXIV. TEM results revealed clear mitophagy-autophagosomes nearly absent p62 LC3B treatment. Furthermore, increased FUNDC1 transgenic or AD-like cell model, luckily, it restoring II/I ratio vitro.ConclusionThe findings suggest dysfunction enhancing reduced injury.

Language: Английский

Concurrent diffusion of nicotinic acetylcholine receptors and fluorescent cholesterol disclosed by two-colour sub-millisecond MINFLUX-based single-molecule tracking

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Nicotinic acetylcholine receptors (nAChRs) are ubiquitous neurotransmitter predominantly located at the cell-surface of neurons and muscle cells. Their dynamics affect synaptogenesis neurodevelopmental stages efficacy synaptic transmission in adult synapse. Here we exploit enhanced capabilities superresolution fluorescence MINFLUX microscopy to track for minute-long periods with nanometric precision sub-millisecond time resolution 2D translational bungarotoxin-labelled muscle-type nAChR tandem a fluorescent cholesterol analogue. To this end, implemented multiplexing procedure continuous that enabled simultaneous excitation two molecules using single wavelength, followed by discrimination their emissions via differential ratiometric recording. Single-molecule trajectories displayed heterogeneous spectrum diffusive behaviours (subdiffusive, Brownian superdiffusive), predominance subdiffusive component, which became less pronounced upon depletion. nAChRs spent most lifetime confined areas characteristic size (~ 0.005 µm²) lasting ~ 100 ms. Further, captured regions where moved jointly, both confinement sojourns along free walks, strongly indicated mutual interactions between receptor macromolecule neutral lipid. best our knowledge, study constitutes first series experiments showing diffusion transmembrane protein -a functionally important receptor- together key membrane lipid native plasma live cell such high detail, thanks MINFLUX-based recordings.

Language: Английский

Role of Neural Circuits in Cognitive Impairment

Neurochemical Research, Journal Year: 2024, Volume and Issue: 50(1)

Published: Dec. 7, 2024

Language: Английский