Lu Huan-Jun, Lv Jing
Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Jiangsu 226019, China.
Department of Physiology, Hebei University of Engineering, Hebei 056000, China.
Exp Neurobiol. 2021 Apr 30;30(2):144-154. doi: 10.5607/en20058.
Sleep deprivation (SD) leads to cognitive impairment, especially hippocampus-dependent learning and memory (L&M). The hippocampal dentate gyrus (DG) is the key structure involved in spatial L&M while long-term potentiation (LTP) is an important cellular mechanism responsible for L&M. Physiological and behavioral evidences support the hypothesis that norepinephrine (NE) and β-adrenoceptors (β-AR) may play an important role in regulating L&M, including LTP. However, it is enigmatic how β-AR influences the LTP disruption or memory impairment under SD circumstances. In the present study, the rats were subjected to SD for 18 h per day for 21 consecutive days and cognitive capacity was assessed by the Morris water maze (MWM) test. We examined the extracellular concentration of NE in the DG using brain microdialysis and HPLC analysis. The amplitudes of field excitatory postsynaptic potential (fEPSP) were subsequently measured in the DG during MWM test in freely moving conscious rats. The extracellular concentrations of NE and fEPSP amplitudes in the DG were significantly increased during MWM test, while these responses were suppressed in SD rats. When fEPSP amplitudes in the DG were measured after local injection of isoproterenol (an agonist of β-AR), SD rats significantly alleviated the fEPSP impairment and rescued deficits of spatial L&M. In addition, the reduced expression of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in SD rats significantly increased by activation of β-AR by isoproterenol in the DG. In conclusion, we propose that β-adrenergic signaling can improve memory impairment in sleep-deficient rats by regulating synaptic efficiency and glutamatergic receptor expression.
睡眠剥夺（SD）会导致认知障碍，尤其是依赖海马体的学习和记忆（L&M）。海马齿状回（DG）是参与空间学习和记忆的关键结构，而长时程增强（LTP）是负责学习和记忆的重要细胞机制。生理和行为证据支持去甲肾上腺素（NE）和β-肾上腺素能受体（β-AR）可能在调节学习和记忆（包括LTP）中起重要作用的假说。然而，在睡眠剥夺情况下β-AR如何影响LTP破坏或记忆损伤仍不清楚。在本研究中，大鼠连续21天每天接受18小时的睡眠剥夺，并通过莫里斯水迷宫（MWM）测试评估认知能力。我们使用脑微透析和高效液相色谱分析检测了DG中NE的细胞外浓度。随后在自由活动的清醒大鼠进行MWM测试期间，测量了DG中的场兴奋性突触后电位（fEPSP）幅度。在MWM测试期间，DG中NE的细胞外浓度和fEPSP幅度显著增加，而在睡眠剥夺大鼠中这些反应受到抑制。当在局部注射异丙肾上腺素（β-AR的激动剂）后测量DG中的fEPSP幅度时，睡眠剥夺大鼠显著减轻了fEPSP损伤并挽救了空间学习和记忆缺陷。此外，睡眠剥夺大鼠中N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体的表达降低，通过在DG中用异丙肾上腺素激活β-AR而显著增加。总之，我们提出β-肾上腺素能信号传导可以通过调节突触效率和谷氨酸能受体表达来改善睡眠不足大鼠的记忆损伤。
