Ewa Rojczyk1, Artur Pałasz2, Ryszard Wiaderkiewicz2. 1. Department of Histology, Faculty of Medicine in Katowice, Medical University of Silesia, Katowice, Poland. Electronic address: ewarojczyk@gmail.com. 2. Department of Histology, Faculty of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Abstract
BACKGROUND: Among many factors influencing adult neurogenesis, pharmacological modulation has been broadly studied. It is proven that neuroleptics positively affect new neuron formation in canonical neurogenic sites - subgranular zone of the hippocampal dentate gyrus and subventricular zone of the lateral ventricles. Latest findings suggest that adult neurogenesis also occurs in several additional regions like the hypothalamus, amygdala, neocortex and striatum. As the hypothalamus is considered an important target of neuroleptics, a hypothesis can be made that these substances are able to modulate local neural proliferation. METHODS: Experiments were performed on adult male rats injected for 28 days or 1 day by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Immunohistochemistry was used to determine expression of proliferation marker (Ki-67) and the marker of neuroblasts - doublecortin (DCX) - which may inform about drug influence on adult neurogenesis at the level of the hypothalamus. RESULTS: It was shown that a single injection of antipsychotics causes significant decrease in hypothalamic DCX expression, but after chronic treatment with chlorpromazine, but not olanzapine, there is an increase in the number of newly formed neuroblasts. Haloperidol has the opposite effect - its long-term administration decreases the number of DCX-positive cells. Cell proliferation levels (Ki-67 expression) increase after long-term drug administration, whereas their single doses do not have any modulatory effect on proliferation potential. CONCLUSIONS: Our results throw a new light on the neuroleptics mechanism of action. They also support the potential role of antipsychotics as a factor that can modulate hypothalamic neurogenesis with putative clinical applications.
BACKGROUND: Among many factors influencing adult neurogenesis, pharmacological modulation has been broadly studied. It is proven that neuroleptics positively affect new neuron formation in canonical neurogenic sites - subgranular zone of the hippocampal dentate gyrus and subventricular zone of the lateral ventricles. Latest findings suggest that adult neurogenesis also occurs in several additional regions like the hypothalamus, amygdala, neocortex and striatum. As the hypothalamus is considered an important target of neuroleptics, a hypothesis can be made that these substances are able to modulate local neural proliferation. METHODS: Experiments were performed on adult male rats injected for 28 days or 1 day by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Immunohistochemistry was used to determine expression of proliferation marker (Ki-67) and the marker of neuroblasts - doublecortin (DCX) - which may inform about drug influence on adult neurogenesis at the level of the hypothalamus. RESULTS: It was shown that a single injection of antipsychotics causes significant decrease in hypothalamicDCX expression, but after chronic treatment with chlorpromazine, but not olanzapine, there is an increase in the number of newly formed neuroblasts. Haloperidol has the opposite effect - its long-term administration decreases the number of DCX-positive cells. Cell proliferation levels (Ki-67 expression) increase after long-term drug administration, whereas their single doses do not have any modulatory effect on proliferation potential. CONCLUSIONS: Our results throw a new light on the neuroleptics mechanism of action. They also support the potential role of antipsychotics as a factor that can modulate hypothalamic neurogenesis with putative clinical applications.
Authors: Artur Pałasz; Aleksandra Suszka-Świtek; Jacek Francikowski; Marek Krzystanek; Katarzyna Bogus; Jakub Skałbania; John J Worthington; Inga Mrzyk Journal: Pharmaceuticals (Basel) Date: 2021-03-27