Ketamine interferes with the proliferation and differentiation of neural stem cells in the subventricular zone of neonatal XXXX .

@entity35 @entity4124 @entity40
BACKGROUND: Previous studies have shown ketamine can alter the proliferation and differentiation of neural stem cells (NSCs) in vitro. However, these effects have not been entirely clarified in vivo in the subventricular zone (SVZ) of neonatal @entity35 . The present study was designed to investigate the effects of ketamine on the proliferation and differentiation of NSCs in the SVZ of neonatal @entity35 in vivo. METHODS: Postnatal day 7 (PND-7) male @entity35 were administered four injections of 40 mg/kg ketamine at 1-h intervals, and then 5-bromodeoxyuridine (BrdU) was injected intraperitoneally at PND-7, 9 and 13. NSC proliferation was assessed with Nestin/BrdU double-labeling immunostaining. Neuronal and astrocytic differentiation was evaluated with b-tubulin III/BrdU and @entity40 /BrdU double-labeling immunostaining, respectively. The expressions of nestin, @entity40 were measured using Western blot analysis. The apoptosis of NSCs and astrocytes in the SVZ of neonatal @entity35 was evaluated using nestin/ @entity4124 and @entity40 / @entity4124 double-labeling immunostaining. RESULTS: Neonatal ketamine exposure significantly reduced the number of nestin/BrdU and @entity40 /BrdU double-positive cells in the SVZ. Meanwhile, the expressions of nestin and @entity40 in the SVZ from the ketamine group were significantly decreased compared those in the control group. Still, no double-positive cells for nestin/ @entity4124 and @entity40 / @entity4124 were found after ketamine exposure. In addition, the neuronal differentiation of NSCs in the SVZ was markedly promoted by ketamine with an increased number of b-tubulin III/BrdU double-positive cells and enhanced expression of b-tubulin III. These effects of ketamine on the NSCs in the SVZ often lasted at least 1 week after ketamine anesthesia. CONCLUSION: In the present study, it was demonstrated that ketamine could alter neurogenesis by inhibiting the proliferation of NSCs, suppressing their differentiation into astrocytes and promoting the neuronal differentiation of the NSCs in the SVZ of neonatal @entity35 during a critical period of their neurodevelopment.    2015 S. Karger AG, Basel.
