Rao Muddanna Sakkattu, Abd-El-Basset Ebtesam M
Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait, Kuwait.
Front Behav Neurosci. 2020 Mar 5;14:18. doi: 10.3389/fnbeh.2020.00018. eCollection 2020.
Dibutyryl cyclic adenosine monophosphate (dBcAMP) is a cell-permeable synthetic analog of cyclic adenosine monophosphate (cAMP). Although the elevation of cAMP levels was reported to promote the functional recovery in spinal cord injury, its role in neurogenesis or functional recovery after hippocampal injury is unknown. The objective of the study was to investigate the effects of dBcAMP on learning, memory, and hippocampal neurogenesis in the excitotoxically lesioned hippocampus. An excitotoxic lesion was induced in the hippocampi of 4-month-old male BALB/c mice by injecting 0.25 μg/μl into the lateral ventricles of both sides. The lesioned mice (L) were divided into L+dBcAMP and L+phosphate-buffered saline (PBS) groups. Sham surgery (S) was done by the injection of 1 μl of sterile saline into the lateral ventricles. The sham surgery mice were divided into S+dBcAMP and S+PBS groups. Mice in the L+dBcAMP and S+dBcAMP groups were treated with dBcAMP for 1 week (i.p., 50 mg/kg), whereas mice in the L+PBS and S+PBS groups were treated with PBS. The mice in all groups were subjected to water maze and passive avoidance tests at the end of the 4th week. Cresyl violet staining and NeuN and doublecortin immunostaining were done to analyze the morphology and neurogenesis. The water maze learning sessions did not show a significant difference in escape latency between the groups, suggesting an unimpaired learning ability of mice in all groups. The L+dBcAMP mice had significantly short entry latency and higher target quadrant time/distance traveled compared to the L+PBS group, suggesting better memory retention. The L+dBcAMP group had a significantly improved memory retention compared to the L+PBS mice during the passive avoidance test. Morphological studies showed significantly greater adult neurons and increased hippocampal neurogenesis in the hippocampus of mice in the L+dBcAMP group compared to those in the L+PBS group. There was no significant difference between the S+dBcAMP and S+PBS groups in the water maze/passive avoidance tests and the number of neurons. In conclusion, dBcAMP protects the hippocampal neuron from degeneration and enhances hippocampal neurogenesis, learning, and memory.
二丁酰环磷腺苷（dBcAMP）是一种可透过细胞膜的环磷腺苷（cAMP）合成类似物。尽管据报道cAMP水平升高可促进脊髓损伤后的功能恢复，但其在海马损伤后的神经发生或功能恢复中的作用尚不清楚。本研究的目的是探讨dBcAMP对兴奋性毒性损伤海马的学习、记忆和海马神经发生的影响。通过向4月龄雄性BALB/c小鼠双侧侧脑室注射0.25μg/μl诱导兴奋性毒性损伤。损伤小鼠（L）分为L+dBcAMP组和L+磷酸盐缓冲盐水（PBS）组。假手术（S）通过向侧脑室注射1μl无菌生理盐水进行。假手术小鼠分为S+dBcAMP组和S+PBS组。L+dBcAMP组和S+dBcAMP组小鼠用dBcAMP治疗1周（腹腔注射，50mg/kg），而L+PBS组和S+PBS组小鼠用PBS治疗。第4周结束时，对所有组的小鼠进行水迷宫和被动回避试验。进行甲酚紫染色以及NeuN和双皮质素免疫染色以分析形态和神经发生情况。水迷宫学习阶段各组之间逃避潜伏期无显著差异，表明所有组小鼠的学习能力未受损。与L+PBS组相比，L+dBcAMP组小鼠的进入潜伏期明显缩短，目标象限时间/行进距离更高，表明记忆保持更好。在被动回避试验中，L+dBcAMP组与L+PBS组小鼠相比，记忆保持能力显著提高。形态学研究表明，与L+PBS组相比，L+dBcAMP组小鼠海马中成年神经元显著增多，海马神经发生增加。S+dBcAMP组和S+PBS组在水迷宫/被动回避试验和神经元数量方面无显著差异。总之，dBcAMP可保护海马神经元免于退化，并增强海马神经发生、学习和记忆。
