Effects of the cannabinoid 1 receptor peptide ligands hemopressin, (m) RVD-hemopressin(alpha) and (m)VD-hemopressin(alpha) on memory in novel object and object location recognition tasks in normal young and A beta(1-42)-treated mice
Effects of the cannabinoid 1 receptor peptide ligands hemopressin, (m) RVD-hemopressin(alpha) and (m)VD-hemopressin(alpha) on memory in novel object and object location recognition tasks in normal young and A beta(1-42)-treated mice
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大麻素 1 受体肽配体加压素、(m) RVD-加压素 (α) 和 (m)VD-加压素 (α) 对正常年轻人和 A beta 中新物体和物体位置识别任务中记忆的影响 (1-42)
DOI：
10.1016/j.nlm.2016.07.030
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发表时间：
2016
影响因子：
2.7
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Zhang Rui-san;He Zhen;Jin Wei-dong;Wang Rui;Zhang Rui-san;Wang R
大麻素系统在记忆过程中起着重要的作用，许多研究表明大麻素受体配体具有调节啮齿动物记忆的能力。非肽类血加压素(HP)来源于大鼠脑内，可作为大麻素1(CB1)受体的多肽拮抗剂或选择性逆多肽激动剂。从小鼠脑中分离的Hp的N-末端延伸形式，(M)rvd-血加压素(α)(Rvd)和(M)vd-血加压素(α)(Vd)也作为多肽激动剂与cb1受体结合。在这里，我们使用新的物体识别(NOR)和物体位置识别(OLR)任务来研究HP、RVD和VD对小鼠记忆的作用。训练前注射HP不仅能改善记忆形成，而且能延长任务中的记忆保持时间，这些作用可被相同剂量的RVD或VD所抑制。在给予HP前15min注射CB1受体小分子激动剂WIN55,212-215min可抑制HP的记忆改善作用。此外，在相同的实验条件下，i.c.v.RVD或VD表现出记忆损伤效应，HP(i.c.v.)训练前14天注射淀粉样蛋白β(1-42)(Aβ1-42)可导致小鼠记忆障碍，可作为阿尔茨海默病(AD)的动物模型。在这些小鼠中，RVD或VD(i.c.v.)能逆转Aβ1-42所致的记忆障碍，并可被HP(i.c.v.)或AM251(2 mg/kg，ip)。上述结果提示，HP、β和VD作为CB1受体多肽配体，可能与AD一样，成为治疗记忆障碍的潜在药物。
The cannabinoid system plays an important role in memory processes, many studies have indicated that cannabinoid receptor ligands have ability to modulate memory in rodents. A nonapeptide hemopressin (Hp) derived from rat brain, acts as a peptide antagonist or selective inverse peptide agonist of cannabinoid 1 (CB1) receptor. N-terminally extended forms of Hp isolated from mouse brain, (m)RVD-hemopressin(α) (RVD) and (m)VD-hemopressin(α) (VD) also bind CB1 receptor, however, as peptide agonists. Here, we investigated the roles of Hp, RVD, and VD on memory in mice using novel object recognition (NOR) and object location recognition (OLR) tasks.In normal young mice, intracerebroventricular (i.c.v.) infusion of Hp before training not only improved memory formation, but also prolonged memory retention in the tasks, these effects could be inhibited by RVD or VD at the same dose and intraperitoneal (i.p.) injection of a small molecule agonist of CB1 receptor WIN55, 212-2 15 min before administration of Hp inhibited the memory-improving effect of Hp. In addition, under the same experimental conditions, i.c.v. RVD or VD displayed memory-impairing effects, which could be prevented by Hp (i.c.v.) or AM251 (i.p.), a small molecule antagonist of CB1 receptor.Infusion of amyloid-β (1–42) (Aβ1–42) 14 days before training resulted in impairment of memory in mice which could be used as animal model of Alzheimer’s disease (AD). In these mice, RVD or VD (i.c.v.) reversed the memory impairment induced by Aβ1–42, and the effects of RVD and VD could be suppressed by Hp (i.c.v.) or AM251 (2 mg/kg, i.p.). Separate administration of Hp had no effect in Aβ1–42-treated mice.The above results suggested that Hp, RVD and VD, as CB1 receptor peptide ligands, may be potential drugs to treatment of the memory deficit-involving disease, just as AD.