Ketamine affects the integration of developmentally generated granule neurons in the adult stage
Background Ketamine has been reported to cause neonatal neurotoxicity in a variety of developing animal models. Various studies have been conducted to study the mechanism of neurotoxicity for general anesthetic use during the neonatal period. Previous experiments have suggested that developmentally generated granule neurons in the hippocampus dentate gyrus (DG) supported hippocampus-dependent memory. Therefore, this study aimed to investigate whether ketamine affects the functional integration of developmentally generated granule neurons in the DG. For this purpose,the postnatal day 7 (PND-7) Sprague-Dawley (SD) rats were divided into the control group and the ketamine group (rats who received 4 injections of 40 mg/kg ketamine at 1 h intervals). To label dividing cells, BrdU was administered for three consecutive days after the ketamine exposure; NeuN+/BrdU+ cells were observed by using immunofluorescence. To evaluate the developmentally generated granule neurons that support hippocampus-dependent memory, spatial reference memory was tested by using Morris Water Maze at 3 months old, after which the immunofluorescence was used to detect c-Fos expression in the NeuN+/BrdU+ cells. The expression of caspase-3 was measured by Western blot to detect the apoptosis in the hippocampal DG.ResultsThe present results showed that the neonatal ketamine exposure did not influence the survival rate of developmentally generated granule neurons at 2 and 3 months old, but ketamine interfered with the integration of these neurons into the hippocampal DG neural circuits and caused a deficit in hippocampal-dependent spatial reference memory tasks.ConclusionsIn summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.
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Posted 18 Dec, 2019
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Ketamine affects the integration of developmentally generated granule neurons in the adult stage
Posted 18 Dec, 2019
On 18 Dec, 2019
On 06 Dec, 2019
On 05 Dec, 2019
On 04 Dec, 2019
On 04 Dec, 2019
On 03 Dec, 2019
On 21 Nov, 2019
On 20 Nov, 2019
Invitations sent on 16 Nov, 2019
On 31 Oct, 2019
On 30 Oct, 2019
On 30 Oct, 2019
Received 25 Oct, 2019
On 25 Oct, 2019
Received 11 Oct, 2019
On 16 Sep, 2019
On 11 Sep, 2019
Invitations sent on 11 Sep, 2019
On 11 Sep, 2019
On 10 Sep, 2019
On 10 Sep, 2019
On 12 Aug, 2019
Received 09 Aug, 2019
Received 28 Jul, 2019
On 26 Jul, 2019
On 15 Jul, 2019
Invitations sent on 23 Jun, 2019
On 17 Jun, 2019
On 17 Jun, 2019
On 17 Jun, 2019
Background Ketamine has been reported to cause neonatal neurotoxicity in a variety of developing animal models. Various studies have been conducted to study the mechanism of neurotoxicity for general anesthetic use during the neonatal period. Previous experiments have suggested that developmentally generated granule neurons in the hippocampus dentate gyrus (DG) supported hippocampus-dependent memory. Therefore, this study aimed to investigate whether ketamine affects the functional integration of developmentally generated granule neurons in the DG. For this purpose,the postnatal day 7 (PND-7) Sprague-Dawley (SD) rats were divided into the control group and the ketamine group (rats who received 4 injections of 40 mg/kg ketamine at 1 h intervals). To label dividing cells, BrdU was administered for three consecutive days after the ketamine exposure; NeuN+/BrdU+ cells were observed by using immunofluorescence. To evaluate the developmentally generated granule neurons that support hippocampus-dependent memory, spatial reference memory was tested by using Morris Water Maze at 3 months old, after which the immunofluorescence was used to detect c-Fos expression in the NeuN+/BrdU+ cells. The expression of caspase-3 was measured by Western blot to detect the apoptosis in the hippocampal DG.ResultsThe present results showed that the neonatal ketamine exposure did not influence the survival rate of developmentally generated granule neurons at 2 and 3 months old, but ketamine interfered with the integration of these neurons into the hippocampal DG neural circuits and caused a deficit in hippocampal-dependent spatial reference memory tasks.ConclusionsIn summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5