Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats
Authors Zhang Y, Gao Q, Wu Z, Xue H, Liu B, Zhao P
Received 22 August 2019
Accepted for publication 2 December 2019
Published 3 January 2020 Volume 2019:13 Pages 4439—4449
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Qiongyu Guo
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 China
Correspondence: Ping Zhao
Department of Anesthesiology, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, People’s Republic of China
Background: 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
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