Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Central Nervous System Source Modulates Microglia Function and Morphology In Vitro

Version 1 : Received: 30 March 2023 / Approved: 31 March 2023 / Online: 31 March 2023 (04:09:06 CEST)

A peer-reviewed article of this Preprint also exists.

Pinho, A.G.; Monteiro, A.; Fernandes, S.; de Sousa, N.; Salgado, A.J.; Silva, N.A.; Monteiro, S. The Central Nervous System Source Modulates Microglia Function and Morphology In Vitro. Int. J. Mol. Sci. 2023, 24, 7685. Pinho, A.G.; Monteiro, A.; Fernandes, S.; de Sousa, N.; Salgado, A.J.; Silva, N.A.; Monteiro, S. The Central Nervous System Source Modulates Microglia Function and Morphology In Vitro. Int. J. Mol. Sci. 2023, 24, 7685.

Abstract

Regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new hints on microglia heterogeneity across central nervous system (CNS) regions are still being unraveled by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on in vitro behavior by applying the same experimental protocol and culture conditions. We analyzed microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in spinal cord-derived glial cultures, presenting different expression of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-. Morphologically, cortical microglial cells are more complex and present longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired in the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.

Keywords

microglia; cortex; spinal cord; morphology; phagocytosis; in vitro studies

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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