First and second generation antipsychotics differentially affect structural and functional properties of rat hippocampal neuron synapses.
The therapy of patients suffering the psychiatric disorder schizophrenia requires the usage of antipsychotic drugs that are classified into two different groups, the first-generation (FGAs) and the second-generation antipsychotics (SGAs). This study compares the effects of the two FGAs haloperidol and flupentixol with those of the SGA olanzapine on synapse formation and synaptic activity of embryonic rat hippocampal neurons. To this end, the development of perineuronal nets (PNNs), the formation of synapses and the resulting spontaneous network activity under control and treatment conditions were studied using an indirect co-culture system of neurons and astrocytes in completely defined media. The number and extent of PNNs that consist of extracellular matrix superstructures surrounding synapses was not altered in hippocampal neurons by exposure to antipsychotic drugs. In contrast treatment of hippocampal neurons with haloperidol led to a slight decrease whereas olanzapine induced a significant increase of the number of structural synapses after 13days. This differential effect concerning synapse numbers was also reflected in the spontaneous activity of neuronal networks, as monitored on multielectrode arrays (MEAs). In that context, application of haloperidol reduced while olanzapine significantly enhanced network activity. Unexpectedly, flupentixol that is regarded as an FGA caused similar effects than the SGA olanzapine in that it augmented synapse number as well as network activity. Our pilot study provides a proof of concept that the neuron-astrocyte co-culture model can be used to investigate the impact of antipsychotics on pivotal parameters of neuronal cell biology. Thereby, it may support the comparative analysis of antipsychotics applied in the therapy of schizophrenia.
Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, D-44780 Bochum, Germany.
Christine
C
Gottschling
Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, D-44780 Bochum, Germany.
Maren
M
Geissler
Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, D-44780 Bochum, Germany.
Gianna
G
Springer
Department of Psychiatry, LWL-University Hospital, Ruhr-University Bochum, D-44791 Bochum, Germany.
Rainer
R
Wolf
Department of Psychiatry, LWL-University Hospital, Ruhr-University Bochum, D-44791 Bochum, Germany.
Georg
G
Juckel
Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, D-44780 Bochum, Germany. Electronic address: andreas.faissner@rub.de.
Andreas
A
Faissner
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001569:Benzodiazepines / Q000494:pharmacology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000502:physiology; D000077152:Olanzapine; D051381:Rats; D012559:Schizophrenia / Q000139:chemically induced; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine
astrocyte; extracellular matrix; indirect co-culture system; neuron-glia interaction; perineuronal net; synapse formation