Dysregulation of Immune Mediators and Synaptic Plasticity in Central Nervous System Disorders

Bidirectional communication between the central nervous system and the immune system is crucial for brain function, particularly in regulating neuroplasticity: on the one hand, glial cells modulate neuronal function, brain circuitry, axon myelination, dendritic spine architecture, and information processing, while on the other hand, neuronal activity can alter the immune response. Neuroinflammation and dysregulation of astroglia and microglia can be detrimental to brain development and function. In particular, maladaptive responses and chronic glial activation have been correlated to synaptic dysfunction in diverse brain conditions. In the present review, we will provide a general introduction to the main players of the neuroimmune response and their ability to modulate neuroplasticity, followed by a comprehensive overview of experimental evidence linking the dysregulation of immune mediators to the disruption of synaptic plasticity in neurodegenerative and neurodevelopmental disorders, with a specific focus on Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder.