High expression of miR-124 improves cognitive function of sleep-deprived rats by modulating the PI3K/AKT signaling pathway

doi:10.12122/j.issn.1673-4254.2025.02.15

Abstract

Abstract:

Objective To explore the molecular mechanism by which miR-124 affects cognitive function of sleep-deprived rats. Methods Fifty-four adult male SD rats were randomized into 6 groups (n=9), including a normal control group, a sleep deprivation (SD) model group, and 4 intracerebral microinjection groups in which the rats were subjected to stereotactic injection of miR-124 agomir, miR-124 agomir NC, miR-124 antagomir, or miR-124 antagomir into the lateral ventricle 7 days before SD modeling. The cognitive functions of the rats were evaluated with Morris water maze test, and pathological changes in the hippocampus were observed using HE staining. The expression level of miR-124 in hippocampal tissues of the rats was detected with qRT-PCR, and the expression level of apoptosis-related proteins and signaling pathway proteins were determined using Western blotting. Results In Morris water maze test, the SD rat models treated with miR-124 agomir showed a significantly shorter escape latency and fewer platform crossings with increased percentage of time and swimming distance in the fourth quadrant as compared with those in SD model group, while the rats treated with miR-124 antagomir exhibited worsened performance in the test. In the SD rat models, treatment with miR-124 agomir obviously lessened pathological changes in the hippocampus, while treatment with miR-124 antagomir significantly worsened the pathological changes. Compared with those in SD model group, the miR-124 agomir-treated rats showed an increased hippocampal expression of miR-124 with upregulated protein expressions of PI3K, p-AKT/AKT, and Bcl-2 and downregulated expressions of Bax and caspase-3 proteins, while rats treated with miR-124 antagomir showed significantly decreased hippocampal expression of miR-124 with lowered expressions of PI3K, p-AKT/AKT and Bcl-2 proteins and increased Bax and caspase-3 protein expressions. Conclusion High expression of miR-124 alleviates SD-induced cognitive decline and neuronal apoptosis in rats by activating the PI3K/AKT signaling pathway.

Key words: sleep deprivation, miR-124, PI3K/AKT signaling pathway, cognitive function, rats

Yuejiao PEI, Huimin LIU, Yu XIN, Bo LIU. High expression of miR-124 improves cognitive function of sleep-deprived rats by modulating the PI3K/AKT signaling pathway[J]. Journal of Southern Medical University, 2025, 45(2): 340-346.

Figures/Tables 7

References 27

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Group	Initial BW(g)	Final BW(g)
CC	267.2±24.4	296.0±22.7
SD	269.7±24.9^a	245.2±20.0^b
SD+miR-124 agomir	268.2±28.0^a	241.3±26.7^b
SD+agomir NC	268.8±32.9^a	242.8±28.6^b
SD+miR-124 antagomir	284.7±26.1^a	259.2±26.5^b
SD+antagomir NC	277.5±20.8^a	255.0±20.4^b
F	0.345	3.558
P	0.881	0.012

Group	Initial BW(g)	Final BW(g)
CC	267.2±24.4	296.0±22.7
SD	269.7±24.9^a	245.2±20.0^b
SD+miR-124 agomir	268.2±28.0^a	241.3±26.7^b
SD+agomir NC	268.8±32.9^a	242.8±28.6^b
SD+miR-124 antagomir	284.7±26.1^a	259.2±26.5^b
SD+antagomir NC	277.5±20.8^a	255.0±20.4^b
F	0.345	3.558
P	0.881	0.012

Groups	Escape latency (s)	Number of crossings through the original platform	Percentage of target quadrant dwell time (%)	Target quadrant distance percentage (%)
CC	4.23±0.88	8.17±1.67	0.37±0.02	0.35±0.02
SD	14.91±4.09^a	4.50±0.96^a	0.24±0.03^a	0.23±0.03^a
SD+miR-124 agomir	6.39±1.42^b	6.83±1.57^b	0.33±0.01^b	0.31±0.01^b
SD+agomir NC	14.32±5.85^ac	4.83±1.07^ac	0.25±0.02^ac	0.23±0.02^ac
SD+miR-124 antagomir	32.46±8.86^ab	2.00±0.58^ab	0.16±0.02^ab	0.16±0.02^ab
SD+antagomir NC	13.04±4.54^ad	4.17±1.07^ad	0.24±0.02^ad	0.24±0.02^ad
F	19.469	15.890	58.233	52.981
P	<0.001	<0.001	<0.001	<0.001

Groups	Escape latency (s)	Number of crossings through the original platform	Percentage of target quadrant dwell time (%)	Target quadrant distance percentage (%)
CC	4.23±0.88	8.17±1.67	0.37±0.02	0.35±0.02
SD	14.91±4.09^a	4.50±0.96^a	0.24±0.03^a	0.23±0.03^a
SD+miR-124 agomir	6.39±1.42^b	6.83±1.57^b	0.33±0.01^b	0.31±0.01^b
SD+agomir NC	14.32±5.85^ac	4.83±1.07^ac	0.25±0.02^ac	0.23±0.02^ac
SD+miR-124 antagomir	32.46±8.86^ab	2.00±0.58^ab	0.16±0.02^ab	0.16±0.02^ab
SD+antagomir NC	13.04±4.54^ad	4.17±1.07^ad	0.24±0.02^ad	0.24±0.02^ad
F	19.469	15.890	58.233	52.981
P	<0.001	<0.001	<0.001	<0.001

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