マイクロバブル超音波技術を用いたmiR-96-5p阻害薬の脳内送達による神経保護効果およびミクログリア活性化への影響

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  • The effect of a miR-96-5p inhibitor delivery to brain using microbubbles and ultrasound technology on neuroprotection and microglial activation

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<p>Glutathione (GSH) is an important antioxidant that plays a critical role in neuroprotection. GSH depletion in neuron induces oxidative stress promoting neuronal damage, which is regarded as a hallmark of the early stage in some neurodegenerative diseases, such as Alzheimer&apos;s disease and Parkinson&apos;s disease. The neuronal GSH levels are mainly regulated by excitatory amino acid carrier 1 (EAAC1) and its inhibitory protein, glutamate transporter-associated protein 3-18 (GTRAP3-18). In this study, we found that GTRAP3-18 levels were increased by the up-regulation of the microRNA miR-96-5p, which has been reported to decrease EAAC1 levels in our previous study. We also discovered that neuro-oncological ventral antigen 1 (NOVA1) is an intermediate protein for GTRAP3-18 expression via miR-96-5p. Moreover, we show that the administration of a miR-96-5p-inhibiting nucleic acid to living mice by a drug delivery system using microbubbles and ultrasound decreased the levels of GTRAP3-18 via NOVA1, while increased the levels of both EAAC1 and GSH in the mouse brain. Although the treatment of microbubbles and ultrasound itself increased microglial activation, the administration of miR-96-5p inhibitor decreased its activation. These findings suggest that the delivery of a miR-96-5p inhibitor to the brain would efficiently increase the neuroprotective activity by increasing GSH levels via EAAC1, GTRAP3-18 and NOVA1.</p>

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