Matsuda S, Peng H, Yoshimura H, Wen T C, Fukuda T, Sakanaka M
Department of Anatomy, Ehime University School of Medicine, Japan.
Neurosci Res. 1996 Oct;26(2):157-70.
The present study was conducted to demonstrate immunohistochemically, the sites of c-fos protein expression in the brains of mice subjected to acute and chronic social defeat stress. To induce social stress, mice were placed in situations of species-specific intermale aggression either only once or five times at 24 h intervals. Two hours after the single or fifth defeat stress, many c-fos immunoreactive neurons were observed in a variety of brain regions including the limbic system and sensory relay nuclei. The c-fos immunoreactive neurons in the brains of acute defeat mice decreased in number with time and the c-fos staining pattern of acute defeat mice became indistinguishable from that of normal control mice by 24 h after the single defeat stress. In contrast, chronic defeat stress induced persistent c-fos expression in the forebrain and brainstem even 24 h after the fifth defeat stress. In the forebrain of chronic defeat mice, the olfactory bulb, cingulate cortex, hippocampus, entire hypothalamus, septal nuclei and the amygdaloid complex, except for the central nucleus, were labeled intensely with c-fos antiserum. In the lower brainstem, nerve cells with c-fos immunoreactivity were seen mainly in ascending and descending sensory relay nuclei relevant to auditory and vestibular transmission, epicritic sensation (gracile and external cuneate nuclei), pain inhibition (central gray and raphe nuclei), and viscerosensory transmission (solitary tract nucleus). The differences in c-fos expression among the normal control, acute and chronic defeat mice were evaluated by an enumeration of the immunopositive neurons within each brain nucleus examined, and they were confirmed subsequently by statistical analysis. There was little c-fos expression in the nucleus putamen, lateral, ventral and posterior thalamic nuclei, pretectal nuclei, medial geniculate nucleus, red nucleus, substantia nigra, cerebellum, spinal cord, or cranial nerve nuclei. These findings suggest that chronic but not acute defeat stress causes persistent c-fos expression in more widespread brain regions than do any other stresses so far investigated. The present study may shed light on the central mechanisms by which behavioral abnormalities and/or chronic sociopsychological stress leads to the occurrence of abnormal behavior and/or psychosomatic disorders in experimental animals and humans.
本研究旨在通过免疫组织化学方法，证明遭受急性和慢性社会挫败应激的小鼠大脑中c-fos蛋白的表达部位。为了诱导社会应激，将小鼠置于种内雄性间攻击的情境中，单次或每隔24小时进行5次。在单次或第5次挫败应激后2小时，在包括边缘系统和感觉中继核在内的多种脑区观察到许多c-fos免疫反应性神经元。急性挫败小鼠大脑中的c-fos免疫反应性神经元数量随时间减少，单次挫败应激后24小时，急性挫败小鼠的c-fos染色模式与正常对照小鼠难以区分。相比之下，慢性挫败应激即使在第5次挫败应激后24小时仍在前脑和脑干中诱导持续的c-fos表达。在慢性挫败小鼠的前脑中，嗅球、扣带回皮质、海马、整个下丘脑、隔核以及杏仁复合体（中央核除外）被c-fos抗血清强烈标记。在脑干下部，具有c-fos免疫反应性的神经细胞主要见于与听觉和前庭传导、精细感觉（薄束核和楔外核）、疼痛抑制（中央灰质和中缝核）以及内脏感觉传导（孤束核）相关的升、降感觉中继核。通过对每个检查脑核内的免疫阳性神经元进行计数，评估正常对照、急性和慢性挫败小鼠之间c-fos表达的差异，随后通过统计分析进行确认。壳核、丘脑外侧核、腹侧核和后核、顶盖前核、内侧膝状体核、红核、黑质、小脑、脊髓或脑神经核中几乎没有c-fos表达。这些发现表明，慢性而非急性挫败应激比迄今为止研究的任何其他应激在更广泛的脑区引起持续的c-fos表达。本研究可能有助于阐明行为异常和/或慢性社会心理应激导致实验动物和人类出现异常行为和/或身心障碍的中枢机制。
