NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis

Koganezawa, Noriko; Sekino, Yuko; Kawakami, Haruo; Fuchino, Hiroyuki; Kawahara, Nobuo; Shirao, Tomoaki

doi:10.1111/ejn.15231

Cited by 4 publications

(2 citation statements)

References 37 publications

(72 reference statements)

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“…Other compounds, like onjisaponin B, can elevate the expression of neurotrophic factors ( Yabe et al, 2003 ). Tenuifolin directly impacts synaptic status ( Koganezawa et al, 2021 ), increasing the total length and intersection numbers of dendrites in hippocampal CA1 neurons, notably affecting only female mice ( Kong et al, 2024 ). Brain-derived neurotrophic factor (BDNF) is known to activate LTP and increase dendritic spine formation, thus potentially reversing LTP deficits.…”

Section: Pharmacological Effects Of Saponin Compoundsmentioning

confidence: 99%

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Li,

Hou,

et al. 2024

Front. Pharmacol.

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ObjectiveThis study aims to elucidate the intervention effects of saponin components from Polygala tenuifolia Willd (Polygalaceae) on dementia, providing experimental evidence and new insights for the research and application of saponins in the field of dementia.Materials and MethodsThis review is based on a search of the PubMed, NCBI, and Google Scholar databases from their inception to 13 May 2024, using terms such as “P. tenuifolia,” “P. tenuifolia and saponins,” “toxicity,” “dementia,” “Alzheimer’s disease,” “Parkinson’s disease dementia,” and “vascular dementia.” The article summarizes the saponin components of P. tenuifolia, including tenuigenin, tenuifolin, polygalasaponins XXXII, and onjisaponin B, as well as the pathophysiological mechanisms of dementia. Importantly, it highlights the potential mechanisms by which the active components of P. tenuifolia prevent and treat diseases and relevant clinical studies.ResultsThe saponin components of P. tenuifolia can reduce β-amyloid accumulation, exhibit antioxidant effects, regulate neurotransmitters, improve synaptic function, possess anti-inflammatory properties, inhibit neuronal apoptosis, and modulate autophagy. Therefore, P. tenuifolia may play a role in the prevention and treatment of dementia.ConclusionThe saponin components of P. tenuifolia have shown certain therapeutic effects on dementia. They can prevent and treat dementia through various mechanisms.

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Section: Pharmacological Effects Of Saponin Compoundsmentioning

confidence: 99%

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Li,

Hou,

et al. 2024

Front. Pharmacol.

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“…By conducting a high-content analysis using drebrin as readout, we have recently reported the inhibitory effects of phencyclidine analogs on N-methyl-D-aspartic acidtype glutamate receptors (NMDARs) 10 and the NMDAR-dependent effects of natural compounds and crude drugs on synaptic states 15 .…”

Section: Introductionmentioning

confidence: 99%

Easy and Reproducible Low-Density Primary Culture using Frozen Stock of Embryonic Hippocampal Neurons

Koganezawa

Roppongi

Sekino

et al. 2023

JoVE

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Neuronal culture is a valuable system for evaluating synaptic functions and drug screenings. In particular, a low-density culture of primary hippocampal neurons allows the study of individual neurons or subcellular components. We have shown subcellular protein localization within a neuron by immunocytochemistry, neuronal polarity, synaptic morphology, and its developmental change using a low-density primary hippocampal culture. Recently, ready-to-use frozen stocks of neurons have become commercially available. These frozen stocks of neurons reduce the time needed to prepare animal experiments and also contribute to the reduction of the number of animals used. Here, we introduce a reproducible low-density primary culture method using a 96-well plate. We used a commercially available frozen stock of neurons from the rat embryonic hippocampus. The neurons can be stably cultured long-term without media changes by reducing the growth of glial cells at particular timepoints. This high-throughput assay using low-density culture allows reproducible imaging-based evaluations of synaptic plasticity.

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NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis

Koganezawa

Sekino

Kawakami

et al. 2021

Eur J of Neuroscience

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Effective drugs that can cure cognitive impairments remain elusive. Because synaptic dysfunction has been correlated with cognitive impairments, drug development to target synaptic dysfunction is important. Recently, natural compounds and crude drugs have emerged as potential therapeutic agents for cognitive disorders. However, their effects on synaptic function remain unclear, because of lack of evaluation system with high reproducibility. We have recently developed highly reproducible in vitro high‐content imaging analysis system for evaluation of synaptic function using drebrin as a marker for synaptic states. Therefore, we aimed to examine the direct effects of well‐known natural compounds and crude drugs on synaptic states using this system. Rat hippocampal neurons were treated using natural compounds (nobiletin, diosgenin and tenuifolin) and crude drugs (Uncaria Hook [UH], Bezoar Bovis [BB], Coptis Rhizome [CR], Phellodendron Bark [PB] and Polygala Root [PR]). Immunocytochemical analysis was performed, and dendrite lengths and drebrin cluster densities were automatically quantified. We found that diosgenin, tenuifolin, CR, PB and PR decreased drebrin cluster densities, and the effects of PB and PR were partially dependent on N‐methyl‐D‐aspartic acid‐type glutamate receptors (NMDARs). Nobiletin and UH did not show any effects, whereas low‐dose BB treatment increased drebrin cluster densities. Our results showed that diosgenin, tenuifolin, BB, CR, PB and PR appeared to directly change synaptic states. Particularly, the NMDAR dependency of PB and PR appears to affect synaptic plasticity.

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NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis

Cited by 4 publications

References 37 publications

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Easy and Reproducible Low-Density Primary Culture using Frozen Stock of Embryonic Hippocampal Neurons

NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis

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