Microglia-mediated synaptic pruning as a key deficit in neurodevelopmental disorders: Hype or hope?

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Microglia are recognized for their role in synaptic pruning and neuronal network maturation during neurodevelopment.
• A growing association links microglial deficits to neurodevelopmental disorders (NDDs).
• However, rodent studies and clinical data challenge this direct link, as altered microglia don't always cause NDD phenotypes.

Purpose of the Study:

• To critically evaluate the indispensable role of microglia in healthy neurodevelopment.
• To discuss the area- and age-dependent functions of microglia in synaptic pruning.
• To propose an updated model of microglia-mediated synaptic pruning in NDDs and explore therapeutic potential.

Main Methods:

• Critical review of existing literature on microglia function in neurodevelopment.
• Analysis of rodent studies and clinical data on microglial deficits and NDDs.
• Development of a conceptual model for microglia-mediated synaptic pruning in NDDs.

Main Results:

• Evidence suggests that reduced microglia numbers or altered functions do not invariably lead to overt NDD phenotypes.
• Neuropsychiatric symptoms associated with microglial alterations may manifest primarily in adulthood.
• The role of microglia in synaptic pruning is complex, showing dependency on specific brain areas and developmental age.

Conclusions:

• The necessity of microglia for all aspects of healthy neurodevelopment remains debatable.
• An updated model highlights area- and age-dependent microglia functions in synaptic pruning relevant to NDDs.
• Targeting microglia presents a potential therapeutic avenue for neurodevelopmental disorders.