Neuroinflammatory aspects of early life malnutrition and the impacts on the refinement of neural circuitry and plasticity

Communication between the nervous and immune systems plays a critical role during brain development. Under physiological conditions, microglia and astrocytes act as major players in developmental processes such as neurogenesis, axon outgrowth, synaptic formation, pruning, myelination and neural plasticity. However, chronic or excessive immune activation contributes to glial dysfunction and major disruption of synaptic pruning and adjustment of developing neural circuitry. Thus, inflammatory insults such as maternal infection, metabolic stress, or malnutrition such as lack essential nutrients ( omega-3 fatty acids or tryptophan) or an excess of saturated fat and/or ultra processed foods, alter inflammatory markers leading to abnormal microglial/astrocytic activation. Together, those findings underscore the dual nature of neuroinflammation as both a regulator of normal development and a driver of abnormal development when dysregulated. Understanding how neural, immune and metabolic cues converge to influence glial and neuronal function is essential for developing strategies to prevent or mitigate the long-term consequences of early-life malnutrition on successful brain development during critical periods of post-natal life.