Propofol Administration During Early Postnatal Life Suppresses Hippocampal Neurogenesis

• Published in: Molecular neurobiology Vol. 53; no. 2; pp. 1031 - 1044
• Main Authors: Huang, Jing, Jing, Sheng, Chen, Xi, Bao, Xiaohang, Du, Zhiyong, Li, Hong, Yang, Tiande, Fan, Xiaotang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2016; Springer Nature B.V
• Subjects: Anesthesia; Animals; Animals, Newborn; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Brain; Bromodeoxyuridine - metabolism; Cell Biology; Cell Cycle - drug effects; Cell Line; Cell Proliferation - drug effects; Dendritic Spines - drug effects; Dendritic Spines - metabolism; Dentate Gyrus - drug effects; Dentate Gyrus - pathology; Enzyme Activation - drug effects; Female; Hippocampus - drug effects; Hippocampus - physiology; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - metabolism; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neurobiology; Neurogenesis; Neurology; Neurosciences; Neurotoxicity; Propofol - administration & dosage; Propofol - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Rodents; Signal Transduction - drug effects; SOXB1 Transcription Factors - metabolism; Neurotoxicity; Propofol; Mouse; Neurogenesis; Hippocampus
• DOI: 10.1007/s12035-014-9052-7
• ISSN: 0893-7648; 1559-1182

Propofol is currently one of the most widely used intravenous anesthetics and has been indicated to induce cognitive dysfunction in adults. Here, we investigated the effects of propofol exposure during early postnatal life on hippocampal neurogenesis. Propofol (30 or 60 mg/kg) was administered to mice on either postnatal day (P) 7 or P7–P9; cell proliferation and neurogenesis in the dentate gyrus (DG) were evaluated on P8 or P17. It showed that exposure to propofol on P7 decreased hippocampal cell proliferation as indicated by BrdU and Sox2 immunostaining at P8 in propofol treatment at the dosage of 60 mg/kg but not at the dosage of 30 mg/kg. Western blots revealed propofol treatment decreased Akt or extracellular signal-related kinase (ERK) 1/2 phosphorylation in the hippocampus at P8. Propofol treatment on P7 to P9 reduced the numbers of newly formed neurons in the DG at P17, which was accompanied by delay of granule neuron maturation and decreased the density of dendritic spines, particularly the mushroom-shaped mature spines. Furthermore, the in vitro findings indicated propofol suppressed cell proliferation and cell mitosis and activated apoptosis of C17.2 neural stem cell line in a dose-dependent manner. These findings suggest that propofol impairs cell proliferation and inhibits neurogenesis in the immature mouse brain and thus is possibly involved in the cognitive dysfunction induced by propofol anesthesia.