β-adrenergic Receptor Activity in the Hippocampal Dentate Gyrus Participates in Spatial Learning and Memory Impairment in Sleep-deprived Rats

Abstract

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 in vivo 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-Daspartate (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.

Lycopene Prevents Phthalate-Induced Cognitive Impairment via Modulating Ferroptosis

“…The water maze consisted of a plastic plinth, which was submerged about 2.0 cm underwater in the first quadrant and served as a hidden platform. The detailed method refers to the previous study . The detailed treatment description is outlined in Supplementary 1.1.…”

“…The detailed method refers to the previous study. 37 The detailed treatment description is outlined in Supplementary 1.1.…”

Neural consequences of chronic sleep disruption

“…In addition to loss of LCn, there is evidence of reduced LCn noradrenergic output in adult rats in response to chronic sleep loss. Rats exposed to 3 weeks of sleep fragmentation using a sweeping bar have reduced levels of extracellular noradrenaline in the hippocampus in response to a spatial learning task, relative to control animals [40]. Because levels were measured immediately after sleep disruption, it is unclear whether this reduction in noradrenaline represents persistent dysfunction.…”

Sleep–Wake Disorders in Alzheimer’s Disease: A Review

“…A study in SD rats showed that learning and memory could be improved through activation of β-AR. In this process, the synaptic plasticity is enhanced, and the expressions of NMDA receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor are increased . Notably, NE is also involved in anti-inflammatory response, and it can contribute to the degradation of Aβ in microglia though regulation of the mouse formyl peptide receptor 2 and insulin-degrading enzyme .…”

“…In this process, the synaptic plasticity is enhanced, and the expressions of NMDA receptor and αamino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor are increased. 138 Notably, NE is also involved in antiinflammatory response, and it can contribute to the degradation of Aβ in microglia though regulation of the mouse formyl peptide receptor 2 and insulin-degrading enzyme. 139 Neuroinflammation may be regarded as a mediator that contributes the abnormal LC-NE system to AD development (Figure 2).…”