Hypothermia induced by anesthesia regulates various signals expressions in the hippocampus of animals

Abstract

Though important for a variety of medical procedures, general anesthesia is not a problem free. Some anesthetics have been suggested to affect a number of signals, which are associated with memory consolidation and cognition. In the present study, we attempted to investigate the molecular mechanism of anesthesia-regulated processes. We found that under hypothermic condition, anesthetic of isoflurane enhances various signals expression in hippocampus, including Hspd1, Actb, Mgst1, THBS4, Syp, C1QC, Serpine, Plat, and Ngf, which were related to cellular stress, neural plasticity responses, and hippocampal injury. Importantly, isoflurane and propofol anesthesia reduced fibroblast growth factor (FGF2) and activity-regulated cytoskeleton-associated protein (Arc) expressions, enhanced glial fibrillary acidic protein (GFAP), Iba1 and phosphorylated-Eukaryotic elongation factor 2 (eEF2) levels as well as down-regulated mitogen-activated protein kinases (MAPKs) family members, including p38, ERK1/2 and JNK, in the hippocampus of animals. Moreover, the in vivo cold water swimming (CWS) experiment and in vitro hypothermic incubation of cells further confirmed our hypothesis that hypothermia is tightly linked to the reduction of FGF2 and Arc, augment of GFAP, Iba1 and p-eEF2, and the decreasing of MAPKs. Generally, our study provided new insights into the modulation of various signals by anesthesia-triggered hypothermia.

Introduction

General anesthesia plays an important role in various medical procedures. However, it is not free of problems. General anesthesia is reported to induce learning deficits and influence memory [1], [2]. In addition, it induces pernicious effects on the neurogenesis of hippocampus [3]. General anesthesia causes severe complications, known as molecular events in central nervous system (CNS). Additionally, general anesthesia leads to the alterations of numerous genes expression in different regions of brain [4]. Nevertheless, it is still not fully understood of anesthesia-caused molecular changes.

Various studies reported that hypothermia could result in memory disruption in various organisms including rodents [5]. For instance, cooling leads to memory loss in rats [6]. Several studies indicated that protein synthesis, transcriptions or translation are involved in hypothermia-induced memory disruption [7], [8]. However, the molecular mechanism about how hypothermia induces memory dysfunction is not understood fully. And hypothermia is a common complication of anesthesia, which could result in negative outcomes. Anesthetic agents affect hypothermia through reducing the hypothalamic thermoregulatory set point for shivering and through increasing the core-to-peripheral heat redistribution by vasodilation, which is a main cause of hypothermia in the short surgical protocols [9], [10]. Isoflurane is a commonly used inhalant anesthetic. The advantages of inhalant agents involve their low blood gas solubility, resulting in both rapid induction of and recovery from anesthesia, minimal hepatic metabolism, and precise control of anesthetic depth [11], [12]. Isoflurane has been reported to reduce adenosine triphosphate (ATP) levels in vitro, which might be associated with hypothermia, as well as the complications induced by hypothermia to organisms [13].

Here in our study, we found that in vivo, during isoflurane anesthesia treatment for short time under hypothermic conditions, FGF2 and Arc were down-regulated, GFAP, Iba1 and p-eEF2 were up-regulated, and p-p38, p-ERK1/2 and p-JNK were all decreased. And in vitro, hypothermic incubation of cells further proved our supposing that hypothermia might be a direct factor, leading to the reduction of FGF2 and Arc, augment of GFAP, Iba1 and p-eEF2, as well as the decreasing of MAPKs family members. Together, our study supplied new molecular insights into the regulation of a variety of signals by anesthesia-induced hypothermia.