Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Precision Pharmacy &Drug Development Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Sci Rep. 2017 Mar 16;7:43594. doi: 10.1038/srep43594.
Sleep disorder is becoming a widespread problem in current society, and is associated with impaired cognition and emotional disorders. Progranulin (PGRN), also known as granulin epithelin precursor, promotes neurite outgrowth and cell survival, and is encoded by the GRN gene. It is a tumor necrosis factor α receptor (TNFR) ligand which is implicated in many central nervous system diseases. However, the role PGRN in sleep disorder remains unclear. In the present study, we found that sleep deprivation (S-DEP) impaired the memory and produced thigmotaxis/anxiety-like behaviors in mice. S-DEP increased the levels of TNFα but decreased PGRN levels in the hippocampus. The intracerebroventricular (ICV) injection of PGRN or intraperitoneal injection of TNFα synthesis blocker thalidomide (25 mg/kg), prevented the memory impairment and anxiety behaviors induced by S-DEP. PGRN treatment also restored dendritic spine density in the hippocampus CA1 region and neurogenesis in hippocampus dentate gyrus (DG). These results indicate that an imbalance between TNFα and PGRN contributes to memory impairment and thigmotaxis/anxiety caused by sleep deprivation.
睡眠障碍在当前社会中变得越来越普遍，与认知障碍和情绪障碍有关。颗粒蛋白前体（PGRN）又称为颗粒素上皮细胞前体，可促进神经突生长和细胞存活，由 GRN 基因编码。它是肿瘤坏死因子-α 受体（TNFR）配体，与许多中枢神经系统疾病有关。然而，PGRN 在睡眠障碍中的作用尚不清楚。在本研究中，我们发现睡眠剥夺（S-DEP）会损害记忆并引起小鼠的触壁癖/焦虑样行为。S-DEP 增加了海马体中 TNFα 的水平，但降低了 PGRN 水平。PGRN 的脑室内（ICV）注射或 TNFα 合成抑制剂沙利度胺（25mg/kg）的腹腔内注射，可预防 S-DEP 引起的记忆障碍和焦虑行为。PGRN 治疗还恢复了海马体 CA1 区的树突棘密度和海马体齿状回（DG）中的神经发生。这些结果表明，TNFα 和 PGRN 之间的失衡导致了睡眠剥夺引起的记忆障碍和触壁癖/焦虑。
