期刊
IZVESTIYA VYSSHIKH UCHEBNYKH ZAVEDENIY-PRIKLADNAYA NELINEYNAYA DINAMIKA
卷 29, 期 3, 页码 421-427出版社
SARATOV STATE UNIV
DOI: 10.18500/0869-6632-2021-29-3-421-427
关键词
HIF-prolyl hydroxylases; neuroprotection; primary hippocampal cultures; hypoxia modeling; network activity
资金
- Russian Foundation for Basic Research [18-015-00391, 0729-2020-0061]
Research shows that influencing HIF activity with PHD inhibitors can enhance cell adaptability to hypoxia. Inhibiting PHD in an in vitro hypoxia model can preserve the connectivity of neuron-glial networks.
Neural network functional activity study and estimation of activity changes in different pathological states (e.g. in hypoxia conditions) is an important scientific task. Hypoxia is one of key damaging factors of various brain pathologies such as stroke, traumatic brain injury, neurodegenerative disease etc. Hypoxia causes structural and functional destruction of neuron-glial networks. The protein calls hypoxia-inducible factor (HIF) is one of the main endogenous molecular regulators of the cell's response to hypoxia. It's functional activity is under the control of HIF-prolyl hydroxylase (protein of the prolyl hydroxylase domain, PHD). Recent studies have shown that we can influence HIF activity using PHD-inhibitors and thus increase the cells adaptability to hypoxia. The aim of this work was to determine the effect of PHD on network characteristics of the functional calcium activity in primary neuronal cultures in hypoxia model in vitro. Methods. We investigated Ca2+ signaling in hippocampal cultures using our recently developed method of processing calcium fluorescence imaging data. It includes signal decomposition into individual cells and network reconstruction of dynamical interactions. Results. Our data reveals that the blockade PHD by compound 4896-3212 (neuradapt) during hypoxia modeling preserves the connectivity of neuron-glial networks in the post-hypoxic period. Conclusion. Pharmacological inhibition of PHD which causes the accumulation of HIF, can be used as an effective approach for therapeutic correction of hypoxic damage.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据