Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood <i>via</i> the Akt/p27 Signaling Pathway.

Hui Hui Miao; Wen Bo Liu; Xin Hao Jiao; Ke Jie Shao; Ying Xuan Yuan; Sha Sha; Qi Qi Zhang; Jing Yan; Yin Ying Sun; Cheng Hua Zhou; Yu Qing WU

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Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood via the Akt/p27 Signaling Pathway.

Author: Hui Hui MIAO ¹ ; Wen Bo LIU ² ; Xin Hao JIAO ² ; Ke Jie SHAO ² ; Ying Xuan YUAN ² ; Sha SHA ² ; Qi Qi ZHANG ² ; Jing YAN ² ; Yin Ying SUN ² ; Cheng Hua ZHOU ³ ; Yu Qing WU ^{4
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Author Information

1. Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
2. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
3. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
4. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China
5. NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Publication Type:Journal Article
Keywords: Akt; Hippocampal dentate gyrus; Neurogenesis; Propofol; p27
MeSH: Animals; Cell Proliferation; Hippocampus/metabolism*; Neural Stem Cells; Propofol/toxicity*; Proto-Oncogene Proteins c-akt/metabolism*; Rats; Rats, Sprague-Dawley; Signal Transduction
From: Biomedical and Environmental Sciences 2022;35(4):283-295
CountryChina
Language:English
Abstract: Objective:Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established.
Methods:SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). The expression of p-Akt and p27 were measured by western blotting. The Morris water maze, novel object recognition test, and object location test were used to evaluate neurocognitive function 2-month-old rats.
Results:Phosphorylation of Akt was inhibited, while p27 expression was enhanced after neonatal exposure to propofol. Propofol also inhibited proliferation of neural stem cells (NSCs) and decreased differentiation to neurons and astroglia. Moreover, the neurocognitive function in 2-month-old rats was weakened. Of significance, intra-hippocampal injection of the Akt activator, SC79, attenuated the inhibition of p-AKT and increase of p27 expression. SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation. The propofol-induced neurocognition deficit was also partially reversed by SC79.
Conclusion:Taken together, these results suggest that neurogenesis is hindered by neonatal propofol exposure. Specifically, neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.