Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.

Abstract

Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day (PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway.

• Authors: Yang Lu, P K Giri, Shan Lei, Juan Zheng, Weisong Li, Ning Wang, Xinlin Chen, Haixia Lu, Zhiyi Zuo, Yong Liu, Pengbo Zhang
• Journal: Neuroscience (Neuroscience) Vol. 352 Pg. 144-154 (06 03 2017) ISSN: 1873-7544 [Electronic] United States
• PMID: 28391017 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Doublecortin Domain Proteins
• Excitatory Amino Acid Antagonists
• Glial Fibrillary Acidic Protein
• Microtubule-Associated Proteins
• Neuropeptides
• Tubulin
• Ketamine
• Caspase 3
• Phosphopyruvate Hydratase
• Minocycline
• Bromodeoxyuridine

Topics

• Animals
• Animals, Newborn
• Bromodeoxyuridine
• Caspase 3 (metabolism)
• Doublecortin Domain Proteins
• Drug Administration Schedule
• Excitatory Amino Acid Antagonists (toxicity)
• Glial Fibrillary Acidic Protein (metabolism)
• Hippocampus (drug effects)
• In Situ Nick-End Labeling
• Ketamine (toxicity)
• Lateral Ventricles (drug effects)
• Maze Learning (drug effects)
• Microtubule-Associated Proteins (metabolism)
• Minocycline (pharmacology)
• Neurogenesis (drug effects)
• Neuropeptides (metabolism)
• Phosphopyruvate Hydratase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Tubulin (metabolism)