====== Astrocyte Dysfunction ======

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

===== 🧠 Physiological Roles of Astrocytes =====

  * 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**.

===== ⚠️ Mechanisms of Dysfunction =====

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

===== 🧬 Associated Conditions =====

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

===== 🧪 Experimental Markers and Models =====

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

===== 🔗 Related Concepts =====

  * [[neurovascular_coupling]]
  * [[glutamatergic_neurotransmission]]
  * [[AQP4]]
  * [[SorCS2]]
  * [[excitotoxicity]]
  * [[reactive_astrogliosis]]