ADENOSINE A1 RECEPTOR ANTAGONIST MITIGATES DELETERIOUS EFFECTS OF SLEEP DEPRIVATION ON ADULT NEUROGENESIS AND SPATIAL REFERENCE MEMORY IN RATS
ADENOSINE A1 RECEPTOR ANTAGONIST MITIGATES DELETERIOUS EFFECTS OF SLEEP DEPRIVATION ON ADULT NEUROGENESIS AND SPATIAL REFERENCE MEMORY IN RATS
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DOI：
10.1016/j.neuroscience.2016.09.007
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发表时间：
2016-11-19
期刊：
影响因子：
3.3
通讯作者：
Singh, S. B.
中科院分区：
文献类型：
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作者：
Chauhan, G.;Ray, K.;Singh, S. B.
睡眠剥夺 (SD) 会升高细胞内腺苷水平，损害成人神经元细胞增殖 (NCP) 和认知，而咖啡因（一种非选择性腺苷 A1 受体 (A1R) 拮抗剂）可改善 SD 期间的认知和成人 NCP。我们使用 8-环戊基-1,3-二甲基黄嘌呤 (8-CPT) 检查了腺苷 A1R 在 48 小时 SD 期间对空间参考记忆损伤和成人 NCP 的选择性拮抗作用。成年雄性 Sprague Dawley 大鼠被剥夺睡眠 48 小时，使用基于动物活动的自动笼振动刺激。使用莫里斯水迷宫测试空间参考记忆作为认知表现的衡量标准。每天两次给予大鼠溶解在 50% 二甲基亚砜 (DMSO) 中的 8-喜树碱 (10 mg/kg，腹腔注射) 以及 5-溴-2-脱氧尿苷 (BrdU) (50 mg/kg/天，腹腔注射)。与 SD 大鼠相比，用 8-CPT 治疗的大鼠表现出显着较短的平均潜伏期和到达平台的路径长度。与这些发现一致的是，8-CPT 治疗组的 BrdU、Ki-67 和双皮质素 (DCX) 阳性细胞数量显着增加。然而，齿状回 (DG) 中的 NeuN 表达没有观察到显着差异。 SD 后观察到 DG 和 CA1 区域的脑源性神经营养因子 (BDNF) 表达显着下降，并通过 8-CPT 治疗得到恢复。此外，到达平台的潜伏期与 DG 中 BrdU、DCX 1 型细胞和 BDNF 表达的数量呈负相关。因此，可以得出结论，SD 期间使用 8-CPT（一种腺苷 A1R 拮抗剂）治疗可减轻 SD 诱导的空间参考记忆和成人 NCP 的下降，可能是通过上调 DG 和 CA1 区域的 BDNF 水平来实现的。 (C) 2016 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Sleep deprivation (SD) upsurges intracellular levels of adenosine, impairs adult neuronal cell proliferation (NCP) and cognition while caffeine, a non-selective adenosine A1 receptor (A1R) antagonist improves cognition and adult NCP during SD. We examined the selective antagonistic effects of adenosine A1R using 8-cyclopentyl-1,3-dime thylxanthine (8-CPT) on impairment of spatial reference memory and adult NCP during 48 h SD. Adult male Sprague Dawley rats were sleep deprived for 48 h, using an automatic cage vibrating stimulus based on animal activity. Spatial reference memory was tested as a measure of cognitive performance employing Morris Water Maze. Rats were given 8-CPT dissolved in 50% dimethyl sulfoxide (DMSO), twice daily (10 mg/kg, i.p.) along with 5-bromo-2-deoxyuridine (BrdU) (50 mg/kg/day,i.p.). The rats treated with 8-CPT showed significantly short mean latency and path-length to reach the platform compared to the SD rats. Consistent with these findings, 8-CPT-treated group was found to have significantly increased the number of BrdU, Ki-67 and doublecortin (DCX) positive cells. However, no significant difference was seen in NeuN expression in the Dentate Gyrus (DG). Brain-derived neurotropic factor (BDNF) expression in the DG and CA1 region was observed to decrease significantly after SD and be rescued by 8-CPT treatment. Furthermore, latency to reach platform showed a negative correlation with number of BrdU, DCX type-1 cells and BDNF expression in DG. Thus, it may be concluded that treatment with 8-CPT, an adenosine A1R antagonist during SD mitigates SD induced decline in spatial reference memory and adult NCP possibly via up regulation of BDNF levels in DG and CA1 regions. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.