rTMS reduces spatial learning and memory deficits induced by sleep deprivation possibly via suppressing the expression of kynurenine 3-monooxygenase in rats

Abstract

Introduction: Impairment of learning and memory caused by sleep deprivation is a common symptom that significantly affects quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a promising approach to exert a positive effect on cognitive impairment. However, there is less known about the mechanism of rTMS for learning and memory induced by chronic REM sleep deprivation (CRSD). This study was to detect the effects of rTMS on spatial learning and memory deficits by CRSD and explore possible mechanism.

Methods: Sixty male Sprague-Dawley rats were randomly divided into four groups: wide platform (Control), sleep deprivation (SD), sleep deprivation + rTMS (TMS), and sleep deprivation + sham rTMS (Sham-TMS). Morris water maze (MWM) and open field test (OFT) assessed spatial learning and memory and anxiety of rats with pre/post-intervention. Golgi staining and transmission electron microscope (TEM) were used to observe structural variations of synapses in the hippocampus. The alteration in gene expression of different groups was analyzed by RNA-sequencing (RNA-Seq), and the key gene was screened and identified by quantitative polymerase chain reaction (qPCR) and subsequently verified with western blotting and immunofluorescence.

Results: The behavioral test showed spatial learning and memory decreased and anxiety increased in the SD group compared to the Control and TMS groups. Moreover, rTMS improved spine density, ultrastructural damage, and quantities of synapses. In accordance with RNA-Seq, 56 differentially expressed genes (DEGs) were identified by comparing alternations in four groups and concentrated on kynurenine 3-monooxygenase (KMO). The expression of KMO increased significantly in rats of the SD group compared to the Control and TMS groups identified by qPCR, western blotting, and immunofluorescence.

Conclusion: 1 Hz rTMS alleviated spatial learning and memory deficits induced by CRSD probably via down-regulating the expression of KMO and improving the structure and quantity of synapses in the hippocampus of rats.

Keywords: Hippocampus; Kynurenine 3-monooxygenase; Learning and memory; Sleep deprivation; Transcranial magnetic stimulation.