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

Annika Ahtiainen, Barbara Genocchi, Jarno M. A. Tanskanen, Michael T. Barros, Jari A. K. Hyttinen, Kerstin Lenk

    Research output: Contribution to journalArticleScientificpeer-review

    15 Citations (Scopus)
    9 Downloads (Pure)

    Abstract

    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.
    Original languageEnglish
    Article number12770
    JournalInternational Journal of Molecular Sciences
    Volume22
    Issue number23
    DOIs
    Publication statusPublished - 25 Nov 2021
    Publication typeA1 Journal article-refereed

    Keywords

    • epilepsy
    • 4AP
    • gabazine
    • astrocytes
    • MEA
    • co-culture

    Publication forum classification

    • Publication forum level 1

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