CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness

Abstract

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. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f−/−mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.

Delayed microglial depletion after spinal cord injury reduces chronic inflammation and neurodegeneration in the brain and improves neurological recovery in male mice

“…Although SCI did not alter the number of CD11b + CD45 int microglia in the brain at 7 days post-injury, our data indicate that SCI causes maladaptive transformation of microglia in the cerebral cortex from a neurorestorative or neuroprotective phenotype to a neurotoxic phenotype. The latter may contribute to SCI-mediated depressive-like behavior, which is in agreement with a recent study 82 showing similar changes in microglial phenotype can spur the development of neuropsychiatric diseases, including major depressive disorder. Moreover, NanoString analysis demonstrated that SCI decreased 30 out of a total of 44 differentially expressed genes in the cortex, which was strongly related to neurons and neurotransmission, apoptosis, and microglia function.…”

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

“…Secondly, LTBP-1 targets latent TGF-β1 to the ECM by interacting with different proteins including fibronectin and fibrillin, generating deposits of latent TGF-β1 accessible for cell-mediated activation and regulating cancer cell proliferation and immunity [59]. Immunology homeostasis instabilities may cause deficits of cognitive and memory in human brain, which could be a potential cause of depressive and anxiety disorders [60]. On the other side, as important component of neural microenvironment, ECM could regulate the neural inflammation in central nervous system [61].…”

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

“…Secondly, LTBP-1 targets latent TGF-β1 to the ECM by interacting with different proteins including bronectin and brillin, generating deposits of latent TGF-β1 accessible for cell-mediated activation and regulating cancer cell proliferation and immunity [59]. Immunology homeostasis instabilities may cause de cits of cognitive and memory in human brain, which could be a potential cause of depressive and anxiety disorders [60]. On the other side, as important component of neural microenvironment, ECM could regulate the neural in ammation in central nervous system [61].…”