Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats
Yahan Zhang,1 Qiushi Gao,1 Ziyi Wu,1 Hang Xue,1 Bo Liu,2 Ping Zhao1 1Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China; 2Department of Animal Laboratory of Experimental Research Center, Shengjing Hospital, China Medical Univers...
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Dove Medical Press
2020-01-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/dexmedetomidine-promotes-hippocampal-neurogenesis-and-improves-spatial-peer-reviewed-article-DDDT |
| _version_ | 1818505196154650624 |
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| author | Zhang Y Gao Q Wu Z Xue H Liu B Zhao P |
| author_facet | Zhang Y Gao Q Wu Z Xue H Liu B Zhao P |
| author_sort | Zhang Y |
| collection | DOAJ |
| description | Yahan Zhang,1 Qiushi Gao,1 Ziyi Wu,1 Hang Xue,1 Bo Liu,2 Ping Zhao1 1Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China; 2Department of Animal Laboratory of Experimental Research Center, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Ping ZhaoDepartment of Anesthesiology, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, People’s Republic of ChinaTel +86-189-4025-8971Email zhaoping_sj@163.comBackground: Dexmedetomidine (Dex) is a highly selective α2-adrenoceptor agonist used as an off-label medication for pediatric sedation and analgesia. Recently, Dex was reported to exhibit neuroprotective efficacy in several brain injury models. Here we investigate whether neonatal Dex administration promotes hippocampal neurogenesis and enhances hippocampus-dependent spatial learning and memory under physiological conditions.Methods: Postnatal day 7 (P7) pups were administered saline (vehicle control) or Dex (10, 20, or 40 μg/kg) by intraperitoneal injection. Neurogenesis and astrogenesis were examined in brain slices by BrdU immunostaining on P8 and changes in the expression levels of GDNF, NCAM, CREB, PSD95, and GAP43 were assessed by Western blotting on P35, respectively. Open field and Morris water maze (MWM) tests were conducted from P28 to P36 in order to assess effects on general motor activity and spatial learning, respectively.Results: Dexmedetomidine at 20 μg/kg significantly enhanced neurogenesis and astrogenesis in hippocampus and upregulated GDNF, NCAM, CREB, PSD95, and GAP43 compared to vehicle and other Dex doses. Moreover, 20 μg/kg Dex-injected rats showed no changes in motor or anxiety-like behavior but performed better in the MWM test compared to all other groups.Conclusion: Neonatal injection of Dex (20 μg/kg) enhances spatial learning and memory in rat pups, potentially by promoting hippocampal neurogenesis and synaptic plasticity via activation of GDNF/NCAM/CREB signaling.Keywords: dexmedetomidine, neurogenesis, GDNF, spatial learning and memory, neonate |
| first_indexed | 2024-12-10T21:47:25Z |
| format | Article |
| id | doaj.art-51b5d00dca67412b906262bb543115f6 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-10T21:47:25Z |
| publishDate | 2020-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-51b5d00dca67412b906262bb543115f62022-12-22T01:32:19ZengDove Medical PressDrug Design, Development and Therapy1177-88812020-01-01Volume 134439444950847Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal RatsZhang YGao QWu ZXue HLiu BZhao PYahan Zhang,1 Qiushi Gao,1 Ziyi Wu,1 Hang Xue,1 Bo Liu,2 Ping Zhao1 1Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China; 2Department of Animal Laboratory of Experimental Research Center, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Ping ZhaoDepartment of Anesthesiology, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, People’s Republic of ChinaTel +86-189-4025-8971Email zhaoping_sj@163.comBackground: Dexmedetomidine (Dex) is a highly selective α2-adrenoceptor agonist used as an off-label medication for pediatric sedation and analgesia. Recently, Dex was reported to exhibit neuroprotective efficacy in several brain injury models. Here we investigate whether neonatal Dex administration promotes hippocampal neurogenesis and enhances hippocampus-dependent spatial learning and memory under physiological conditions.Methods: Postnatal day 7 (P7) pups were administered saline (vehicle control) or Dex (10, 20, or 40 μg/kg) by intraperitoneal injection. Neurogenesis and astrogenesis were examined in brain slices by BrdU immunostaining on P8 and changes in the expression levels of GDNF, NCAM, CREB, PSD95, and GAP43 were assessed by Western blotting on P35, respectively. Open field and Morris water maze (MWM) tests were conducted from P28 to P36 in order to assess effects on general motor activity and spatial learning, respectively.Results: Dexmedetomidine at 20 μg/kg significantly enhanced neurogenesis and astrogenesis in hippocampus and upregulated GDNF, NCAM, CREB, PSD95, and GAP43 compared to vehicle and other Dex doses. Moreover, 20 μg/kg Dex-injected rats showed no changes in motor or anxiety-like behavior but performed better in the MWM test compared to all other groups.Conclusion: Neonatal injection of Dex (20 μg/kg) enhances spatial learning and memory in rat pups, potentially by promoting hippocampal neurogenesis and synaptic plasticity via activation of GDNF/NCAM/CREB signaling.Keywords: dexmedetomidine, neurogenesis, GDNF, spatial learning and memory, neonatehttps://www.dovepress.com/dexmedetomidine-promotes-hippocampal-neurogenesis-and-improves-spatial-peer-reviewed-article-DDDTdexmedetomidineneurogenesisgdnfspatial learning and memoryneonate |
| spellingShingle | Zhang Y Gao Q Wu Z Xue H Liu B Zhao P Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats Drug Design, Development and Therapy dexmedetomidine neurogenesis gdnf spatial learning and memory neonate |
| title | Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats |
| title_full | Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats |
| title_fullStr | Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats |
| title_full_unstemmed | Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats |
| title_short | Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats |
| title_sort | dexmedetomidine promotes hippocampal neurogenesis and improves spatial learning and memory in neonatal rats |
| topic | dexmedetomidine neurogenesis gdnf spatial learning and memory neonate |
| url | https://www.dovepress.com/dexmedetomidine-promotes-hippocampal-neurogenesis-and-improves-spatial-peer-reviewed-article-DDDT |
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