Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Neurosci Lett. 2024 Jul 13;835:137851. doi: 10.1016/j.neulet.2024.137851. Epub 2024 Jun 3.
Chronic psychosocial stress stands as a significant heterogeneous risk factor for psychiatric disorders. The brain's physiological response to such stress varies based on the frequency and intensity of stress episodes. However, whether stress episodes divergently could affect hippocampal cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling remains unclear, a key regulator of psychiatric symptoms. We aimed to assess how two distinct patterns of social defeat stress exposure impact anxiety- and depression-like behaviors, fear, and hippocampal CREB-BDNF signaling in adult male rats. To explore this, adult male Sprague-Dawley rats were subjected to psychosocial stress using a Resident/Intruder paradigm for ten consecutive days (continuous social defeat stress: [CS]) or ten social defeat stress over the course of 21 days (intermittent social defeat stress [IS]). Behavioral tests (including novelty-suppressed feeding test, forced swimming test, and contextually conditioned fear) were conducted. Protein expression levels of phosphorylated CREB and BDNF in the dorsal and ventral hippocampi were examined. CS led to heightened anxiety-like behavior, fear, and increased levels of phosphorylated CREB in both the dorsal and ventral hippocampi. Conversely, IS resulted in increased anxiety-like behavior and behavioral despair alongside decreased levels of phosphorylated CREB and BDNF, particularly in the dorsal hippocampus. These findings indicate that chronic psychosocial stress divergently affects hippocampal CREB-BDNF signaling and emotional regulation depending on the stress episode. Such insights could enhance our understanding of the molecular basis of the heterogeneity of psychiatric disorders and facilitate the development of innovative treatment approaches to patients with psychiatric disorders.
慢性心理社会压力是精神障碍的一个重要异质危险因素。大脑对这种压力的生理反应取决于压力发作的频率和强度。然而，压力发作是否会产生差异，从而影响精神症状的关键调节剂——海马环磷酸腺苷反应元件结合蛋白 (CREB)-脑源性神经营养因子 (BDNF) 信号，目前尚不清楚。我们旨在评估两种不同模式的社会挫败应激暴露如何影响成年雄性大鼠的焦虑和抑郁样行为、恐惧和海马 CREB-BDNF 信号。为了探索这一点，成年雄性 Sprague-Dawley 大鼠连续 10 天（连续社会挫败应激：[CS]）或 21 天内进行 10 次社会挫败应激（间歇社会挫败应激：[IS]），使用居民/入侵者范式进行心理社会应激。进行了行为测试（包括新奇抑制喂养测试、强迫游泳测试和情境条件性恐惧）。检查了背侧和腹侧海马中磷酸化 CREB 和 BDNF 的蛋白表达水平。CS 导致焦虑样行为、恐惧增加，以及背侧和腹侧海马中磷酸化 CREB 水平升高。相反，IS 导致焦虑样行为和行为绝望增加，同时背侧海马中磷酸化 CREB 和 BDNF 水平降低。这些发现表明，慢性心理社会应激根据压力发作的不同，对海马 CREB-BDNF 信号和情绪调节产生不同的影响。这些见解可以增强我们对精神障碍异质性的分子基础的理解，并为精神障碍患者开发创新的治疗方法提供帮助。
