Microglia Cells In Brain Disease

By Frontiers in cellular neuroscience - http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00049/full, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=31788649

Microglia cells, immune cells of the central nervous system, are increasingly being linked as involved with a number of brain/neurodegenerative diseases.  This opens up the way for possible therapies; abstract:

There has been an explosion of new findings recently giving us insights into the involvement of microglia in central nervous system (CNS) disorders. A host of new molecular tools and mouse models of disease are increasingly implicating this enigmatic type of nervous system cell as a key player in conditions ranging from neurodevelopmental disorders such as autism to neurodegenerative disorders such as Alzheimer's disease and chronic pain. Contemporaneously, diverse roles are emerging for microglia in the healthy brain, from sculpting developing neuronal circuits to guiding learning-associated plasticity. Understanding the physiological functions of these cells is crucial to determining their roles in disease. Here we focus on recent developments in our rapidly expanding understanding of the function, as well as the dysfunction, of microglia in disorders of the CNS.

Microbiome And Sex-Specific Brain Development

The microbiome can affect microglia development in a sex-specific manner, which has implications for brain development and function.  This occurs in mice, but mouse and human microglia exhibit enough similarities that we can suspect that the same situation holds for humans as well.  This once again demonstrates the profound impacts of microglia, as well as that of sex-specific developmental differences.  Abstract:

Microglia are embryonically seeded macrophages that contribute to brain development, homeostasis, and pathologies. It is thus essential to decipher how microglial properties are temporally regulated by intrinsic and extrinsic factors, such as sexual identity and the microbiome. Here, we found that microglia undergo differentiation phases, discernable by transcriptomic signatures and chromatin accessibility landscapes, which can diverge in adult males and females. Remarkably, the absence of microbiome in germ-free mice had a time and sexually dimorphic impact both prenatally and postnatally: microglia were more profoundly perturbed in male embryos and female adults. Antibiotic treatment of adult mice triggered sexually biased microglial responses revealing both acute and long-term effects of microbiota depletion. Finally, human fetal microglia exhibited significant overlap with the murine transcriptomic signature. Our study shows that microglia respond to environmental challenges in a sex- and time-dependent manner from prenatal stages, with major implications for our understanding of microglial contributions to health and disease.