Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron-Astrocyte Co-Cultures

Int J Mol Sci. 2021 Nov 25;22(23):12770. doi: 10.3390/ijms222312770.


Astrocytes and neurons respond to each other by releasing transmitters, such as γ-aminobutyric acid (GABA) and glutamate, that modulate the synaptic transmission and electrochemical behavior of both cell types. Astrocytes also maintain neuronal homeostasis by clearing neurotransmitters from the extracellular space. These astrocytic actions are altered in diseases involving malfunction of neurons, e.g., in epilepsy, Alzheimer's disease, and Parkinson's disease. Convulsant drugs such as 4-aminopyridine (4-AP) and gabazine are commonly used to study epilepsy in vitro. In this study, we aim to assess the modulatory roles of astrocytes during epileptic-like conditions and in compensating drug-elicited hyperactivity. We plated rat cortical neurons and astrocytes with different ratios on microelectrode arrays, induced seizures with 4-AP and gabazine, and recorded the evoked neuronal activity. Our results indicated that astrocytes effectively counteracted the effect of 4-AP during stimulation. Gabazine, instead, induced neuronal hyperactivity and synchronicity in all cultures. Furthermore, our results showed that the response time to the drugs increased with an increasing number of astrocytes in the co-cultures. To the best of our knowledge, our study is the first that shows the critical modulatory role of astrocytes in 4-AP and gabazine-induced discharges and highlights the importance of considering different proportions of cells in the cultures.

Keywords: 4-AP; MEA; astrocytes; co-cultures; epilepsy; gabazine.

MeSH terms

  • 4-Aminopyridine / pharmacology*
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Coculture Techniques
  • GABA Antagonists / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Potassium Channel Blockers / pharmacology
  • Pyridazines / pharmacology*
  • Rats
  • Synaptic Transmission*


  • GABA Antagonists
  • Potassium Channel Blockers
  • Pyridazines
  • gabazine
  • 4-Aminopyridine