Increased knowledge about brain development and cognitive ability

Cognitive deficiency or decline are common features of neurodevelopmental disorders (such as autism spectrum disorders or attention-deficit/hyperactivity disorder) and neurodegenerative disorders (like Alzheimer disease or dementia). Cognitive capabilities rely heavily on an accurately established and functional neuronal cholinergic system.

In a study published in the journal Nature Neuroscience, an international research team led from the Institute of Environmental Medicine, Karolinska Institutet, Sweden and Universidad de Sevilla, Spain now describes how a particular subset of microglia, the resident immune cells of the brain, which expresses the enzyme Arginase-1, and which they named ARG1⁺microglia, contributes to the establishment of the neuronal cholinergic system during early postnatal mouse development.

Using whole brain imaging, ARG1⁺microglia were found to be located in specific regions of the developing mouse brain, predominantly in the basal forebrain and ventral striatum, where cholinergic neurons are found in large numbers. Genome wide RNA-sequencing analysis demonstrated that ARG1⁺microglia present a distinct gene expression profile, as compared to the ARG1-non expressing microglia. Additional imaging at the ultrastructural level using electron microscopy further revealed that neuronal material was found within the ARG1⁺microglia. Deficiency for the ARG1⁺microglia subtype in mice, was associated with impaired maturation and function of the projections made by cholinergic neurons into the hippocampus, a brain region essential to cognitive functions. Finally, female, but not male, ARG1⁺microglia-deficient mice were shown to exhibit significant cognitive behavioural deficiencies.

Beyond offering of better understanding of the brain development, and the contribution of microglia diversity to that one, the study could provide new cues on how to manage neurodevelopmental disorders or neurodegenerative disorders presenting a cognitive component and often differences between male and female.