Zhang Yahan, Gao Qiushi, Wu Ziyi, Xue Hang, Liu Bo, Zhao Ping
Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Department of Animal Laboratory of Experimental Research Center, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Drug Des Devel Ther. 2019 Dec 31;13:4439-4449. doi: 10.2147/DDDT.S228220. eCollection 2019.
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.
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.
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.
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.
右美托咪定（Dex）是一种高度选择性的α2肾上腺素能受体激动剂，被用作儿科镇静和镇痛的超说明书用药。最近，有报道称右美托咪定在几种脑损伤模型中具有神经保护作用。在此，我们研究在生理条件下，新生大鼠给予右美托咪定是否能促进海马神经发生，并增强海马依赖性空间学习和记忆能力。
出生后第7天（P7）的幼鼠通过腹腔注射给予生理盐水（溶剂对照）或右美托咪定（10、20或40μg/kg）。在出生后第8天，通过BrdU免疫染色检测脑片中的神经发生和星形胶质细胞生成；在出生后第35天，分别通过蛋白质免疫印迹法评估胶质细胞源性神经营养因子（GDNF）、神经细胞黏附分子（NCAM）、环磷腺苷效应元件结合蛋白（CREB）、突触后致密蛋白95（PSD95）和生长相关蛋白43（GAP43）表达水平的变化。分别在出生后第28天至第36天进行旷场试验和莫里斯水迷宫（MWM）试验，以评估对一般运动活动和空间学习的影响。
与溶剂对照和其他右美托咪定剂量相比，20μg/kg的右美托咪定显著增强了海马中的神经发生和星形胶质细胞生成，并上调了GDNF、NCAM、CREB、PSD95和GAP43的表达。此外，与所有其他组相比，注射20μg/kg右美托咪定的大鼠在运动或焦虑样行为方面没有变化，但在MWM试验中表现更好。
新生大鼠注射右美托咪定（20μg/kg）可增强幼鼠的空间学习和记忆能力，可能是通过激活GDNF/NCAM/CREB信号通路促进海马神经发生和突触可塑性来实现的。
