International NF Collaborative Research Reveals Brain Sex Differences

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As part of a Berlin Institute of Health Einstein Fellowship, investigators at the Max Delbrück Center in Berlin worked with NF Center Director, David H. Gutmann, to discover sex differences in microglia function.

In this study, researchers in the laboratory of Professor Helmut Kettenmann found that mouse brain cells, called microglia, react differently to Neurofibromatosis type 1 (NF1) gene mutations. Whereas female mouse microglia function similarly to normal microglia, male Nf1-mutant microglia have prominent defects in their ability to engulf foreign materials (phagocytosis), move in response to injury (motility), and conduct electrical impulses. Importantly, the team found that these defects result from a male-specific Nf1-mutant defect in cyclic AMP signaling.

This exciting work establishes that NF1 mutations can have different effects in males and females, and sets the stage for future studies that aim to determine how sex and genetic mutation intersect to govern clinical outcomes in people with NF1.

The study was recently published in Neurobiology of Disease.

Elmadany N, Logiacco F, Buonfiglioli A, Haage VC, Wright-Jin EC, Schattenberg A, Papawassiliou RM, Kettenmann H, Semtner M, Gutmann DH. Neurofibromatosis 1 – Mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects. Neurobiol Dis. 2020 Oct;144:105030. doi: 10.1016/j.nbd.2020.105030. Epub 2020 Jul 29. PMID: 32736084