| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5737467 | Neuroscience | 2017 | 11 Pages |
•Pretreatment with minocycline increased neurogenesis in the SVZ and SGZ of ketamine-exposed neonatal rats.•Minocycline pretreatment reduced cells apoptosis in SVZ and SGZ, but not frontal cortex of ketamine-exposed neonatal rats.•PI3K/Akt/GSK3β signaling pathway involved in minocycline’s protection on ketamine-induced injury to PND7 rats.•Pretreatment with minocycline improved adult spatial learning and memory deficits induced by ketamine neonatal exposure.
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 30 min 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 12 h 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.
