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基线促肾上腺皮质激素释放激素依赖性和快速眼动睡眠剥夺。

Baseline prepulse inhibition dependency of orexin A and REM sleep deprivation.

机构信息

Department of Molecular Biology and Genetics, Üsküdar University, Istanbul, Turkey.

Faculty of Engineering and Natural Sciences, Üsküdar University Central Campus Block A, Altunizade Mah. Haluk Türksoy Sk. No : 14 34362, Üsküdar, Istanbul, Turkey.

出版信息

Psychopharmacology (Berl). 2024 Jun;241(6):1213-1225. doi: 10.1007/s00213-024-06555-3. Epub 2024 Mar 1.

Abstract

RATIONALE

Prepulse inhibition (PPI) impairment reflects sensorimotor gating problems, i.e. in schizophrenia. This study aims to enlighten the role of orexinergic regulation on PPI in a psychosis-like model.

OBJECTIVES

In order to understand the impact of orexinergic innervation on PPI and how it is modulated by age and baseline PPI (bPPI), chronic orexin A (OXA) injections was carried on non-sleep-deprived and sleep-deprived rats that are grouped by their bPPI.

METHODS

bPPI measurements were carried on male Wistar rats on P45 or P90 followed by grouping into low-PPI and high-PPI rats. The rats were injected with OXA twice per day for four consecutive days starting on P49 or P94, while the control groups received saline injections. 72 h REMSD was carried on via modified multiple platform technique on P94 and either OXA or saline was injected during REMSD. PPI tests were carried out 30 min. after the last injection.

RESULTS

Our previous study with acute OXA injection after REMSD without bPPI grouping revealed that low OXA doses might improve REMSD-induced PPI impairment. Our current results present three important conclusions: (1) The effect of OXA on PPI is bPPI-dependent and age-dependent. (2) The effect of REMSD is bPPI-dependent. (3) The effect of OXA on PPI after REMSD also depends on bPPI.

CONCLUSION

Orexinergic regulation of PPI response with and without REMSD can be predicted by bPPI levels. Our findings provide potential insights into the regulation of sensorimotor gating by sleep/wakefulness systems and present potential therapeutic targets for the disorders, where PPI is disturbed.

摘要

原理

前脉冲抑制 (PPI) 损伤反映了感觉运动门控问题,即精神分裂症。本研究旨在阐明食欲素能调节对类精神病模型中 PPI 的作用。

目的

为了了解食欲素能神经支配对 PPI 的影响,以及它如何被年龄和基础 PPI(bPPI)调节,我们对非睡眠剥夺和睡眠剥夺的大鼠进行了慢性食欲素 A (OXA) 注射,这些大鼠根据其 bPPI 进行分组。

方法

在 P45 或 P90 对雄性 Wistar 大鼠进行 bPPI 测量,然后根据 bPPI 将大鼠分为低 PPI 和高 PPI 大鼠。从 P49 或 P94 开始,每天两次给大鼠注射 OXA,连续四天,而对照组接受盐水注射。在 P94 上通过改良的多个平台技术进行 72 h REMSD,并在 REMSD 期间注射 OXA 或盐水。在最后一次注射后 30 分钟进行 PPI 测试。

结果

我们之前的研究表明,在 REMSD 后急性注射 OXA 而不进行 bPPI 分组时,低剂量 OXA 可能会改善 REMSD 诱导的 PPI 损伤。我们目前的研究结果提出了三个重要结论:(1) OXA 对 PPI 的影响取决于 bPPI 水平和年龄。(2) REMSD 的作用取决于 bPPI。(3) REMSD 后 OXA 对 PPI 的影响也取决于 bPPI。

结论

有或没有 REMSD 的 OXA 对 PPI 反应的调节可以通过 bPPI 水平来预测。我们的发现为睡眠/觉醒系统对感觉运动门控的调节提供了潜在的见解,并为 PPI 受到干扰的疾病提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef1/11106105/db719263ab04/213_2024_6555_Fig1_HTML.jpg

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