Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Laboratory of Environmental Physiology, Faculty of Dental Medicine, The Hebrew University, Jerusalem 9112102, Israel.
Int J Mol Sci. 2022 Apr 8;23(8):4129. doi: 10.3390/ijms23084129.
Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40-41 °C, 2 h) were evaluated in adult male rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment.
暴露在高温环境中是一种应激源,会影响生物和行为功能,并且已经被证明对大脑结构和功能有广泛的影响。本研究评估了成年雄性大鼠在热应激(40-41°C,2 小时)下的生理、细胞和行为反应。研究了热应激暴露(即热应激预处理)对捕食者气味应激(PSS)暴露前的影响。最后,研究了热应激预处理对 PSS 的可能机制。在海马体和下丘脑室旁核(PVN)中进行了选定细胞标志物的免疫组织化学分析。评估了血浆皮质酮水平,行为评估包括高架十字迷宫(EPM)和听觉惊跳反应(ASR)范式。使用氨基酸(L-谷氨酰胺)和药理学试剂(多沙唑嗪)来操纵内源性热休克蛋白(HSP)-70 的水平。单次急性热应激导致体重(BM)下降、体温升高和皮质酮水平升高。此外,还观察到广泛的细胞变化,但没有行为变化。热应激预处理为与 PSS 相关的焦虑样行为提供了行为弹性,这可能是通过诱导 HSP-70 实现的。靶向 HSP-70 是治疗应激相关精神病理学的一种有吸引力的策略。