Ketamine affects the integration of developmentally generated granule neurons in the adult stage

Abstract 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 explore; 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. Results The 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. Conclusions In summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.

Download Full-text

Ketamine affects the integration of developmentally generated granule neurons in the adult stage

BMC Neuroscience ◽

10.1186/s12868-019-0542-4 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Zhanqiang Zhao ◽

Bing Li ◽

Yuqing Wu ◽

Xujun Chen ◽

Yan Guo ◽

...

Keyword(s):

Functional Integration ◽

Reference Memory ◽

Control Group ◽

Granule Neurons ◽

Sprague Dawley ◽

General Anesthetic ◽

Spatial Reference ◽

Spatial Reference Memory ◽

Dividing Cells ◽

Hippocampus Dependent Memory

Abstract 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. Results The 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. Conclusions In summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.

Download Full-text

Ketamine affects the integration of developmentally generated granule neurons in the adult stage

10.21203/rs.2.10461/v4 ◽

2019 ◽

Author(s):

Zhanqiang Zhao ◽

Bing Li ◽

Yuqing Wu ◽

Xujun Chen ◽

Yan Guo ◽

...

Keyword(s):

Functional Integration ◽

Reference Memory ◽

Control Group ◽

Granule Neurons ◽

Sprague Dawley ◽

General Anesthetic ◽

Spatial Reference ◽

Spatial Reference Memory ◽

Dividing Cells ◽

Hippocampus Dependent Memory

Abstract 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.

Download Full-text

Ketamine affects the integration of developmentally generated granule neurons in the adult stage

10.21203/rs.2.10461/v2 ◽

2019 ◽

Author(s):

Zhanqiang Zhao ◽

Bing Li ◽

Yuqing Wu ◽

Xujun Chen ◽

Yan Guo ◽

...

Keyword(s):

Functional Integration ◽

Reference Memory ◽

Control Group ◽

Granule Neurons ◽

Sprague Dawley ◽

General Anesthetic ◽

Spatial Reference ◽

Spatial Reference Memory ◽

Dividing Cells ◽

Hippocampus Dependent Memory

Download Full-text

Ketamine affects the functional convergence of developmentally generated granule neurons in the adult stage

10.21203/rs.2.10461/v1 ◽

2019 ◽

Author(s):

Zhanqiang Zhao ◽

Bing Li ◽

Yuqing Wu ◽

Xujun Chen ◽

Yan Guo ◽

...

Keyword(s):

Functional Integration ◽

Reference Memory ◽

Control Group ◽

Granule Neurons ◽

General Anesthetic ◽

Spatial Reference ◽

Functional Convergence ◽

Spatial Reference Memory ◽

Dividing Cells ◽

Hippocampus Dependent Memory

Abstract 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) 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). The BrdU was administered for three consecutive days after the ketamine exposure. To label the dividing cells, 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. Results The 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. Conclusions In summary, these findings may promote more studies to investigate the neurotoxicity of ketamine in the developing brain.

Download Full-text

Selective H3 Antagonist (ABT-239) Differentially Modifies Cognitive Function Under the Impact of Restraint Stress

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2020.614810 ◽

2021 ◽

Vol 14 ◽

Author(s):

Emil Trofimiuk ◽

Przemysław Wielgat ◽

Halina Car

Keyword(s):

Spatial Memory ◽

Restraint Stress ◽

Reference Memory ◽

Control Group ◽

Memory Impairments ◽

Spatial Reference ◽

Spatial Reference Memory ◽

Pre Treatment ◽

New Compounds ◽

The Impact

Background: A considerable number of competitive antagonists/inverse agonists of histamine H3 receptor (H3R) have progressed to clinical assessment, with pitolisant approved for the treatment of narcolepsy. H3R, highly expressed in the CNS, is regarded as a relevant target in CNS disorders. At the same time, new compounds including ABT-239 H3R antagonist (ABT; benzonitrile, 4-[2-[2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl]-5-benzofuranyl]-) are continually being tested. The study aimed to test ABT-239 as a prophylactic agent in stress-induced memory impairments.Methods: Stressed and non-stressed rats were pre-treated with ABT-239 and subsequently subjected to several behavioral tests aimed at assessing the animals’ working and spatial reference memory [Morris water maze (MWM), Barnes maze (BM)], assessing the locomotor function and anxiety-like behavior [Open field (OF), elevated “plus” maze—EPM].Results: Chronically stressed rats displayed a significant decline in spatial (working and reference) memory. In the MWM test, we observed an improvement in spatial reference memory in stressed animals and a positive after ABT-239 pre-treatment. In the BM test, the effect of ABT-239 administration on spatial memory changed in successive attempts, from negative initially to favorable in subsequent attempts, and negative in the last trial of the test in the control group of rats. However, a beneficial effect is noted in the group of stressed animals, which remained throughout the entire testing period.Conclusions: Presented findings demonstrate that ABT-239 shows the potential to abolish or prevent restraint stress-induced spatial memory impairments and cognitive deficits. However, in conditions of appetitive modulation, it could increase damage to memory (unstressed animals).

Download Full-text

The swimming control group in spatial reference memory task: analysis of its motor cortex activity

ARCHIVES ITALIENNES DE BIOLOGIE ◽

10.12871/00039829202022 ◽

2020 ◽

pp. 45-55

Author(s):

S. Cid-Duarte ◽

A. Gutiérrez-Menéndez ◽

C. Zorzo ◽

J.L. Arias ◽

M. Méndez

Keyword(s):

Motor Cortex ◽

Task Analysis ◽

Memory Task ◽

Reference Memory ◽

Control Group ◽

Spatial Reference ◽

Spatial Reference Memory ◽

Reference Memory Task

Download Full-text

Stingless Bee Honey Improves Spatial Memory in Mice, Probably Associated with Brain-Derived Neurotrophic Factor (BDNF) and Inositol 1,4,5-Triphosphate Receptor Type 1 (Itpr1) Genes

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8258307 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Mohd Zulkifli Mustafa ◽

Fairuz Nabila Zulkifli ◽

Ivanna Fernandez ◽

Abdul Razak Mariatulqabtiah ◽

Muthuraju Sangu ◽

...

Keyword(s):

Gene Expression ◽

Working Memory ◽

Spatial Memory ◽

Spatial Working Memory ◽

Reference Memory ◽

Stingless Bee ◽

Synaptic Function ◽

Control Group ◽

Spatial Reference ◽

Spatial Reference Memory

This study was conducted to evaluate the effects of stingless bee honey (SBH) supplementation on memory and learning in mice. Despite many studies that show the benefits of honey on memory, reports on the nootropic effects of SBH are still lacking, and their underlying mechanism is still unclear. SBH is a honey produced by the bees in the tribe of Meliponini that exist in tropical countries. It features unique storage of honey collected in cerumen pots made of propolis. This SBH may offer a better prospect for therapeutic performance as the previous report identifies the presence of antioxidants that were greater than other honey produced by Apis sp. In this study, SBH was tested on Swiss albino mice following acute (7 days) and semichronic (35 days) supplementation. Experiments were then conducted using Morris water maze (MWM) behaviour analysis, RT-PCR for gene expression of mice striatum, and NMR for metabolomics analysis of the honey. Results indicate spatial working memory and spatial reference memory of mice were significantly improved in the honey-treated group compared with the control group. Improved memory consolidations were also observed in prolonged supplementation. Gene expression analyses of acutely treated mice demonstrated significant upregulation of BDNF and Itpr1 genes that involve in synaptic function. NMR analysis also identified phenylalanine, an essential precursor for tyrosine that plays a role at the BDNF receptor. In conclusion, SBH supplementation for seven days at 2000 mg/kg, which is equivalent to a human dose of 162 mg/kg, showed strong capabilities to improve spatial working memory. And prolonged intake up to 35 days increased spatial reference memory in the mice model. The phenylalanine in SBH may have triggered the upregulation of BDNF genes in honey-treated mice and improved their spatial memory performance.

Download Full-text