Abstract

Neuroimmune Dysregulation and Synaptic Connectivity: The Role of Microglia, Lymphatic Clearance, and EEG Biomarkers in Neurodevelopmental Disorders

Author(s): Gunet Eroglu

Recent studies have illuminated the intricate relationships between microglial activation, synaptic pruning, and the brain’s waste-clearance mechanisms. Synaptic connectivity exists on a spectrum, where one extreme involves excessive synaptic pruning leading to reduced neural connectivity, while the other extreme is characterized by excessive synaptic connectivity due to insufficient pruning. These two extremes can be influenced by factors such as neuroinflammation, immune system function, neurotrophic factor availability, and waste-clearance efficiency. Dysregulation of these processes may lead to various neurological conditions. Excessive microglial activity can lead to heightened synaptic pruning, resulting in increased slow-wave activity across the cortex as in learning disabilities. Concurrently, impairments in the brain’s lymphatic drainage systems may contribute to the accumulation of neurotoxic substances, weakening synaptic connections in specific regions, such as left temporal region in dyslexia. In autism spectrum disorders (ASD), anomalies in the right frontal and motor cortices might be linked to elevated toxicity in adjacent lymphatic structures. Furthermore, deficiencies in the immune system can hinder the clearance of these toxins. Electroencephalogram (EEG) measurements often reflect these underlying pathologies. This review synthesizes recent literature supporting these hypotheses and examines factors contributing to both synaptic degeneration and regeneration.