Imagine your brain as a bustling city with different neighborhoods, each with its own unique characteristics. Within this city, there are special immune cells called microglia and astrocytes that act as the guardians of your brain. In a recent study, scientists took a closer look at how these immune cells respond to a trigger of inflammation, called lipopolysaccharides (LPS). They found that microglia and astrocytes in different brain regions have distinct responses, leading to a region-specific inflammatory reaction. The researchers also evaluated the impact of a particular receptor called CX3CR1 on microglial response and discovered that its partial ablation decreased microglial inflammation. Additionally, they observed variations in the distribution and activation of astrocytes under inflammatory conditions. These findings suggest that the heterogeneity of microglia and astrocytes plays a crucial role in shaping the brain’s immune response. Want to dive deeper into this fascinating research? Check out the full article!

Microglia cells are the macrophage population within the central nervous system, which acts as the first line of the immune defense. These cells present a high level of heterogeneity among different brain regions regarding morphology, cell density, transcriptomes, and expression of different inflammatory mediators. This region-specific heterogeneity may lead to different neuroinflammatory responses, influencing the regional involvement in several neurodegenerative diseases. In this study, we aimed to evaluate microglial response in 16 brain regions. We compared different aspects of the microglial response, such as the extension of their morphological changes, sensitivity, and ability to convert an acute inflammatory response to a chronic one. Then, we investigated the synaptic alterations followed by acute and chronic inflammation in substantia nigra. Moreover, we estimated the effect of partial ablation of fractalkine CX3C receptor 1 (CX3CR1) on microglial response. In the end, we briefly investigated astrocytic heterogeneity and activation. To evaluate microglial response in different brain regions and under the same stimulus, we induced a systemic inflammatory reaction through a single intraperitoneal (i.p.) injection of lipopolysaccharides (LPS). We performed our study using C57BL6 and CX3CR1+/GFP mice to investigate microglial response in different regions and the impact of CX3CR1 partial ablation. We conducted a topographic study quantifying microglia alterations in 16 brain regions through immunohistochemical examination and computational image analysis. Assessing Iba1-immunopositive profiles and the density of the microglia cells, we have observed significant differences in region-specific responses of microglia populations in all parameters considered. Our results underline the peculiar microglial inflammation in the substantia nigra pars reticulata (SNpr). Here and in concomitance with the acute inflammatory response, we observed a transient decrease of dopaminergic dendrites and an alteration of the striato-nigral projections. Additionally, we found a significant decrease in microglia response and the absence of chronic inflammation in CX3CR1+/GFP mice compared to the wild-type ones, suggesting the CX3C axis as a possible pharmacological target against neuroinflammation induced by an increase of systemic tumor necrosis factor-alpha (TNFα) or/and LPS. Finally, we investigated astrocytic heterogeneity in this model. We observed different distribution and morphology of GFAP-positive astrocytes, a heterogeneous response under inflammatory conditions, and a decrease in their activation in CX3CR1 partially ablated mice compared with C57BL6 mice. Altogether, our data confirm that microglia and astrocytes heterogeneity lead to a region-specific inflammatory response in presence of a systemic TNFα or/and LPS treatment.

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