Morphological diversity of microglia: Implications for learning, environmental adaptation, ageing, sex differences and neuropathology

Abstract

Microglia are the brain resident macrophages that respond rapidly to any insult. These non-neuroectodermal cells are decorated with plenty of receptors allowing them to recognise and respond precisely to a multitude of stimuli. To do so, microglia undergo structural and functional changes aiming to actively keep the brain’s homeostasis. However, some microglial responses, when sustained or exacerbated, can contribute to neuropathology and neurodegeneration. Many microglial molecular and cellular changes were identified that display a strong correlation with neuronal damage and neuroinflammation/disease status, as well as present key sex-related differences that modulate microglial outcomes. Nevertheless, the relationship between microglial structural and functional features is just beginning to be unravelled. Several reports show that microglia undergo soma and branch remodelling in response to environmental stimuli, ageing, neurodegenerative diseases, trauma, and systemic inflammation, suggesting a complex form and function link. Also, it is reasonable overall to suppose that microglia diminishing their process length and ramification also reduce their monitoring activity of synapses, which is critical for detecting any synaptic disturbance and performing synaptic remodelling. Elucidating the complex interactions between microglial morphological plasticity and its functional implications appears essential for the understanding of complex cognitive and behavioural processes in health and neuropathological conditions.