Torres-Rodriguez Orlando, Ortiz-Nazario Emily, Rivera-Escobales Yesenia, Velazquez Bethzaly, Colón María, Porter James T
Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico.
Department of Biomedical Sciences, Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico.
Front Behav Neurosci. 2023 Jan 9;16:1014767. doi: 10.3389/fnbeh.2022.1014767. eCollection 2022.
Single prolonged stress (SPS) is a preclinical rodent model for studying post-traumatic stress disorder (PTSD)-like behaviors. Previously we found that increased expression of the microglial marker Iba-1 in the ventral hippocampus after SPS exposure was associated with impaired fear extinction, suggesting that microglial activity contributed to the SPS-induced behavioral changes. To test this, we examined whether reducing microglia with the colony-stimulating factor 1 receptor blocker, PLX3397, in the diet would prevent the SPS-induced extinction impairment. Male rats exposed to SPS showed enhanced fear acquisition and impaired fear extinction memory. Adding PLX3397 to the diet prevented these behavioral changes. In contrast, PLX3397 did not prevent SPS from impairing fear extinction memory in the female rats. Despite the sex-dependent behavioral effects, we found a reduced number and area fraction of Iba-1+ microglia in both male and female rats suggesting that PLX3397 had similar effects on microglia in both sexes. Altogether, these results suggest that microglia contribute to the behavioral changes induced by SPS in male but not female rats.
单次长时间应激（SPS）是一种用于研究创伤后应激障碍（PTSD）样行为的临床前啮齿动物模型。此前我们发现，SPS暴露后腹侧海马中微胶质细胞标志物Iba-1的表达增加与恐惧消退受损有关，这表明微胶质细胞活性促成了SPS诱导的行为变化。为了验证这一点，我们研究了在饮食中使用集落刺激因子1受体阻滞剂PLX3397减少微胶质细胞是否能预防SPS诱导的消退损伤。暴露于SPS的雄性大鼠表现出恐惧习得增强和恐惧消退记忆受损。在饮食中添加PLX3397可预防这些行为变化。相比之下，PLX3397并不能预防SPS对雌性大鼠恐惧消退记忆的损害。尽管存在性别依赖性行为效应，但我们发现雄性和雌性大鼠中Iba-1+微胶质细胞的数量和面积分数均减少，这表明PLX3397对两性的微胶质细胞具有相似的作用。总之，这些结果表明，微胶质细胞促成了SPS在雄性而非雌性大鼠中诱导的行为变化。
