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Amyloid-β slows cilia movement along the ventricle, impairs fluid flow, and exacerbates its neurotoxicity in explant culture

Makibatake, Ryota, Oda, Sora, Yagi, Yoshiki, Tatsumi, Hitoshi·2023·Scientific Reports
DOI 10.1038/s41598-023-40742-0PMC PMC10442439
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Abstract

Alzheimer’s disease (AD) is characterized by extensive and selective death of neurons and deterioration of synapses and circuits in the brain. The Aβ1–42 concentration is higher in an AD brain than in cognitively normal elderly individuals, and Aβ1–42 exhibits neurotoxicity. Brain-derived Aβ is transported into the cerebrospinal fluid (CSF), and CSF flow is driven in part by the beating of cilia and CSF secretion into ventricles. Ventricles are lined with ependyma whose apical surface is covered with motile cilia. Herein, we constructed an experimental system to measure the movement of ependymal cilia and examined the effects of Aβ1–42 to the beating of cilia and neurons. The circadian rhythm of the beating frequency of ependymal cilia was detected using brain wall explant-cultures containing ependymal cilia and neurons; the beating frequency was high at midday and low at midnight. Aβ1–42 decreased the peak frequency of ciliary beating at midday and slightly increased it at midnight. Aβ1–42 exhibited neurotoxicity to neurons on the non-ciliated side of the explant culture, while the neurotoxicity was less evident in neurons on the ciliated side. The neurotoxic effect of Aβ1–42 was diminished when 1 mPa of shear stress was generated using a flow chamber system that mimicked the flow by cilia. These results indicate that Aβ1–42 affects the circadian rhythm of ciliary beating, decreases the medium flow by the cilia-beating, and enhances the neurotoxic action of Aβ1–42 in the brain explant culture.

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  • Aβ exposure directly slows ependymal ciliary beating, impairs ventricular fluid flow, and exacerbates neurotoxicity in explant cultures.

    “A recent study showed that Aβ exposure directly slows ependymal ciliary beating, impairs ventricular fluid flow, and exacerbates neurotoxicity in explant cultures (Makibatake et al., 2023).”

    From Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease (2026) · cites this paper as Makibatake et al., 2023

    The Discussion (page unavailable) reports that Aβ1–42 reduced peak ependymal ciliary beating in rat brain explants and decreased cilia-driven fluid flow. It describes enhanced neurotoxicity from that reduced flow as a possibility, not a demonstrated effect. The measured flow was culture-medium flow, rather than ventricular fluid flow in vivo. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • NSC niches show reduced proliferation and impaired neuronal differentiation, ependymal ciliary activity becomes disrupted, and endothelial dysfunction contributes to BBB breakdown, vascular leakage, and neuroimmune dysregulation.

    “NSC niches show reduced proliferation and impaired neuronal differentiation, ependymal ciliary activity becomes disrupted, and endothelial dysfunction contributes to BBB breakdown, vascular leakage, and neuroimmune dysregulation (Fu et al., 2019; Makibatake et al., 2023; Montagne et al., 2017; Sweeney et al., 2018).”

    From Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease (2026) · cites this paper as Makibatake et al., 2023

  • Disruption of the miR-34/449-CP110 axis could contribute to impaired ventricular cilia and CSF flow, though this has not yet been directly demonstrated in AD tissue.

    “In combination with Aβ-induced ciliary slowing (Makibatake et al., 2023), this suggests that disruption of the miR-34/449-CP110 axis could contribute to impaired ventricular cilia and CSF flow, even though this has not yet been directly demonstrated in AD tissue (Song et al., 2014).”

    From Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease (2026) · cites this paper as Makibatake et al., 2023

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Authors
Makibatake, R., Oda, S., Yagi, Y., & Tatsumi, H.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-08-21
Volume
13
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-023-40742-0
PMC
PMC10442439
Cited by
14
References
2
Language
en
Licence
Funders
Ministry of Education, Culture, Sports, Science, and Technology Japan (JP 21K06102)

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