Alterations in CD300f immunoreceptor are associated to depressive disorder in mice

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD) has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. The CD300f immune receptor has gained attention due to its dual activating and inhibitory signalling motifs. Here, we explored pre-clinical and clinical evidence for the role of this receptor in the fine regulation of microglial phenotype and its effects on MDD. CD300f-/- mice displayed several characteristic MDD traits such as increased microglial numbers, alteration of few innate immunity mediators, and females showed persistent depressive-like and anhedonic behaviours reversible by bupropion treatment, and decreased hippocampal noradrenaline content. Moreover, inhibition of CD300f induced alterations in synaptic strength and synaptogenesis in mixed neuron-glia hippocampal cultures. We performed RNAseq from FACS sorted CD11b+/CD45low cells from female hippocampus. Both naive or LPS treated (2mg/kg) WT or CD300f-/- treated mice were included.