Inhibition of miR-181a protects female mice from transient focal cerebral ischemia by targeting astrocyte estrogen receptor-α

Molecular and Cellular Neurosciences
Creed M StaryR G Giffard

Abstract

Whether the effect of miR-181a is sexually dimorphic in stroke is unknown. Prior work showed protection of male mice with miR-181a inhibition. Estrogen receptor-α (ERα) is an identified target of miR181 in endometrium. Therefore we investigated the separate and joint effects of miR-181a inhibition and 17β-estradiol (E2) replacement after ovariectomy. Adult female mice were ovariectomized and implanted with an E2- or vehicle-containing capsule for 14d prior to 1h middle cerebral artery occlusion (MCAO). Each group received either miR-181a antagomir or mismatch control by intracerebroventricular injection 24h before MCAO. After MCAO neurologic deficit and infarct volume were assessed. Primary male and female astrocyte cultures were subjected to glucose deprivation with miR-181a inhibitor or transfection control, and E2 or vehicle control, with/without ESRα knockdown with small interfering RNA. Cell death was assessed by propidium iodide staining, and lactate dehydrogenase assay. A miR-181a/ERα target site blocker (TSB), with/without miR-181a mimic, was used to confirm targeting of ERα by miR-181a in astrocytes. Individually, miR-181a inhibition or E2 decreased infarct volume and improved neurologic score in female mice, and prote...Continue Reading

Citations

Jul 16, 2020·International Journal of Molecular Sciences·Amela Jusic On Behalf Of The Eu-CardioRNA Cost Action
Feb 1, 2019·International Journal of Molecular Sciences·Shotaro Michinaga, Yutaka Koyama
Oct 31, 2019·Journal of Neuropathology and Experimental Neurology·Vijayaraghava T S RaoSamuel K Ludwin
Mar 27, 2021·Mechanisms of Ageing and Development·Julie A Chowen, Luis M Garcia-Segura
Aug 28, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zeinab VahidiniaMohammad Taghi Joghataei
Jun 1, 2021·Hormone Molecular Biology and Clinical Investigation·Hamideh AbotalebiReyhaneh Shafieian
Sep 28, 2021·Translational Stroke Research·Taylor E BranyanFarida Sohrabji

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