Astrocyte Dysfunction

Astrocyte dysfunction refers to the pathological alteration of astrocytic functions that support neuronal activity, blood-brain barrier integrity, and synaptic regulation.

• Regulation of ion homeostasis (e.g., K⁺ buffering).
• Uptake and recycling of neurotransmitters (especially glutamate via EAATs).
• Modulation of neurovascular coupling through endfoot signaling.
• Maintenance of blood-brain barrier (BBB) via interactions with endothelial cells.
• Participation in synapse formation and pruning.

• Impaired glutamate clearance → excitotoxicity.
• Calcium signaling deficits → disrupted astrocyte-neuron communication.
• AQP4 mislocalization → defective water homeostasis and edema.
• Reactive astrogliosis:
  1. Triggered by injury or inflammation.
  2. Can be protective or contribute to scarring and inhibition of regeneration.
• Metabolic dysfunction: Impaired lactate shuttle and oxidative stress.

• Neurodegenerative diseases:
  1. Alzheimer’s disease
  2. Parkinson’s disease
  3. Amyotrophic lateral sclerosis (ALS)
• Cerebrovascular disease:
  1. Stroke → astrocyte-mediated ischemic damage.
• Epilepsy:
  1. Hyperexcitable networks due to failed K⁺ and glutamate buffering.
• Brain tumors:
  1. Astrocyte-tumor interactions contribute to invasion and microenvironment modulation.

• Markers:
  1. GFAP, S100β, AQP4, EAAT1/2
• Models:
  1. Sorcs2 knockout → impaired calcium signaling and NVC.
  2. Conditional AQP4 deletion → defective water regulation.
  3. GFAP-overexpression mice → study of reactive astrogliosis.

• neurovascular_coupling
• glutamatergic_neurotransmission
• AQP4
• SorCS2
• excitotoxicity
• reactive_astrogliosis