CIRBP ameliorates hypoxia-induced learning and memory deficits in mice by suppressing astrocyte A1 polarization
HUO Xiaodong
ZHAO Fang
WANG Yuchen
WANG Boxuan
HOU Jinchao
GUAN Ruili
ZHOU Yang
CHEN Jingyuan
ZOU Yuankang
Abstract：Objective To investigate whether cold-inducible RNA-binding protein(CIRBP)exerts a protective effect on the learning and memory function of mice exposed to hypoxia by regulating astrocyte A1 polarization in the hippocampus.Methods C57BL/6 mice were randomly divided into 10 groups:(1)normoxic group;(2)normoxia+Lv-NC group(stereotactic injection of Lv-NC negative control lentivirus);(3)normoxia+0.154 mol/L Saline control group(stereotactic injection of normal saline);(4)normoxia+overexpression of CIRBP group(stereotactic injection of CIRBP overexpression lentivirus);(5)normoxia+Zr17-2 group(receptor agonist Zr17-2 intervention);(6)hypoxia group;(7)hypoxia+Lv-NC group(stereotactic injection of Lv-NC negative control lentivirus after hypoxia exposure);(8)hypoxia+0.154 mol/L Saline control group(first exposed to hypoxic environment,and then stereotactic injection of normal saline);(9)hypoxia+overexpression of CIRBP group(after hypoxia exposure,stereotactic injection of CIRBP overexpression lentivirus);(10)hypoxia+Zr17-2 group(after hypoxia exposure,the receptor agonist Zr17-2 was given).All mice were routinely fed after injection,and their learning and memory functions were subsequently detected by Morris water maze and novel object recognition experiments.Western blotting was used to detect the overexpression level of CIRBP in astrocytes in the hippocampus.Immunofluorescence histochemical staining and qRT-PCR were used to detect polarization-related phenotypic changes related to astrocytes A1 in the hippocampus.Results Compared with the normoxic group,the expression level of CIRBP protein in the hippocampus of mice in the hypoxia group was significantly decreased(P<0.01),the expression level of astrocyte A1 polarization in the hippocampus was significantly increased(P<0.01),and the learning and memory ability of mice was significantly decreased(P<0.01).After overexpression of CIRBP or the use of the receptor agonist Zr17-2,compared with the control mice,the expression level of CIRBP protein in the hippocampus of the mice in the treatment group was significantly increased(P<0.01),while the expression level of astrocyte A1 polarization was reduced(P<0.05,P<0.01),and the learning and memory ability of the mice was significantly restored(P<0.05,P<0.01).Conclusion CIRBP protects the learning and memory functions of mice exposed to hypoxia by regulating astrocyte A1 polarization.
Keywords：hypoxialearning and memoryhippocampusastrocytescold-inducible RNA-binding proteinA1 polarizationmicecognitive impairment
Publication Date：2026-05-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：9( 673-681 )