Ora

What causes synaptic dysfunction?

Published in Synaptic Mechanisms 3 mins read

Synaptic dysfunction occurs when the crucial communication points between neurons, known as synapses, fail to function correctly, leading to disruptions in brain activity. This impairment can arise from problems within the synapses themselves or from detrimental changes in their surrounding environment.

Proper synaptic function is essential for all brain activities, including learning, memory, emotions, and movement. When synapses are compromised, it can manifest in a wide range of neurological and psychiatric conditions.

Primary Causes of Synaptic Dysfunction

The underlying reasons for synaptic dysfunction can broadly be categorized into two main areas:


Category Description Key Factors & Examples
1. Intrinsic Synaptic Mechanisms This involves direct alterations to the molecular machinery and structural components that make up the synapse itself. Problems here mean the fundamental processes of neurotransmission are compromised.
  • Genetic Mutations: Defects in genes encoding synaptic proteins (e.g., ion channels, neurotransmitter receptors, scaffolding proteins like PSD-95 or Shank3).
  • Protein Misfolding/Aggregation: Accumulation of abnormal proteins within or around synapses that interfere with their function (e.g., altered protein synthesis or degradation).
  • Impaired Neurotransmitter Dynamics: Issues with the synthesis, release, reuptake, or degradation of neurotransmitters within the synaptic cleft.
  • Structural Abnormalities: Changes in the size, shape, or number of dendritic spines (projections on neurons that receive synaptic input).
2. Extrinsic Environmental Factors These are changes in the biochemical or cellular environment surrounding the synapses that indirectly impair their function. The external milieu becomes toxic or unsupportive, compromising synaptic health and plasticity.
  • Neuroinflammation: Chronic activation of immune cells in the brain (microglia and astrocytes), releasing inflammatory molecules that damage synapses.
  • Oxidative Stress: An imbalance between free radicals and antioxidants, leading to cellular damage, including to synaptic components.
  • Mitochondrial Dysfunction: Impaired energy production within neurons, depriving synapses of the vast energy they require for proper function.
  • Toxic Protein Accumulation: Build-up of misfolded proteins like amyloid-beta plaques and tau tangles (seen in Alzheimer's disease) that disrupt synaptic signaling.
  • Neurotransmitter Imbalances: Systemic or localized imbalances in key neurotransmitters beyond the synapse itself (e.g., chronic glutamate excitotoxicity).
  • Environmental Toxins: Exposure to heavy metals, pesticides, or other neurotoxins that directly or indirectly harm synaptic integrity.
  • Vascular Issues: Reduced blood flow to brain regions, leading to hypoxia or nutrient deprivation, which compromises synaptic viability.
  • Aging: The natural aging process is associated with increased oxidative stress, inflammation, and reduced synaptic plasticity.


Consequences and Related Disorders

Understanding the causes of synaptic dysfunction is crucial because it is a common underlying factor in a wide array of neurological and psychiatric disorders, often referred to as "synaptopathies." These conditions include:

By identifying these varied causes, researchers aim to develop targeted therapeutic strategies to restore synaptic function and alleviate the symptoms of these debilitating conditions.