De Felice Eleonora, Bobotis Bianca Caroline, Rigillo Giovanna, Khakpour Mohammadparsa, Gonçalves de Andrade Elisa, Benatti Cristina, Vilella Antonietta, Tascedda Fabio, Limatola Cristina, Tremblay Marie-Ève, Alboni Silvia, Maggi Laura
Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
Division of Medical Sciences, University of Victoria, Victoria, BC, Canada; Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria, Victoria, BC, Canada.
Brain Behav Immun. 2025 Feb;124:192-204. doi: 10.1016/j.bbi.2024.11.034. Epub 2024 Nov 29.
The hippocampus is a heterogenous structure that exhibits functional segregation along its longitudinal axis. We recently showed that in male mice, microglia, the brain's resident immune cells, differ between the dorsal (DH) and ventral (VH) hippocampus, impacting long-term potentiation (LTP) mainly through the CX3CL1-CX3CR1 signaling. Here, we assessed the specific features of the hippocampal poles in female mice, demonstrating a similar LTP amplitude in VH and DH in both control and Cx3cr1 knock-out mice. In addition, the expression levels of Cx3cr1 and Cx3cl1 mRNA do not differ between the two poles in control mice. These data support the critical role of the CX3CL1-CX3CR1 signaling in setting the physiological amount of plasticity, equally between poles in females. Although BDNF is higher in DH compared to VH, the expression levels of inflammatory markers involved in plasticity and of phagocytosis markers in microglia are comparable between the two poles. In accordance, microglia soma and arborization area/perimeter, and microglial ultrastructure are similar across regions, with the exception of microglial density, cells arborization solidity and circularity that are higher in DH. Understanding the molecular processes underlying microglial sex differences and their potential implications for plasticity in specific brain regions is of major importance in physiological and pathological conditions.
海马体是一种异质性结构，沿其纵轴呈现功能分离。我们最近发现，在雄性小鼠中，作为大脑固有免疫细胞的小胶质细胞在背侧海马体（DH）和腹侧海马体（VH）中存在差异，主要通过CX3CL1-CX3CR1信号通路影响长时程增强（LTP）。在此，我们评估了雌性小鼠海马体两极的具体特征，发现在对照小鼠和Cx3cr1基因敲除小鼠中，VH和DH的LTP幅度相似。此外，对照小鼠两极之间Cx3cr1和Cx3cl1 mRNA的表达水平没有差异。这些数据支持了CX3CL1-CX3CR1信号通路在设定可塑性生理水平方面的关键作用，在雌性小鼠的两极之间作用相同。尽管与VH相比，BDNF在DH中的含量更高，但可塑性相关炎症标志物和小胶质细胞吞噬标志物的表达水平在两极之间相当。相应地，除了小胶质细胞密度、细胞分支坚实度和圆形度在DH中更高外，小胶质细胞的胞体、分支面积/周长以及小胶质细胞超微结构在各区域相似。了解小胶质细胞性别差异背后的分子过程及其对特定脑区可塑性的潜在影响在生理和病理条件下都至关重要。
