Eva Drazanova1, Jana Ruda-Kucerova2, Lucie Kratka3, Katerina Horska4, Regina Demlova5, Zenon Starcuk3, Tomas Kasparek6. 1. Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Institute of Scientific Instruments, The Czech Academy of Sciences, Brno, Czech Republic. 2. Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. Electronic address: jkucer@med.muni.cz. 3. Institute of Scientific Instruments, The Czech Academy of Sciences, Brno, Czech Republic. 4. Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic. 5. Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 6. Department of Psychiatry, University Hospital and Masaryk University, Brno, Czech Republic.
Abstract
BACKGROUND AND PURPOSE: One of the hallmarks of schizophrenia is altered brain structure, potentially due to antipsychotic treatment, the disorder itself or both. It was proposed that functional changes may precede the structural ones. In order to understand and potentially prevent this unwanted process, brain function assessment should be validated as a diagnostic tool. METHODS: We used Arterial Spin Labelling MRI technique for the evaluation of brain perfusion in several brain regions in a neurodevelopmental poly(I:C) model of schizophrenia (8mg/kg on a gestational day 15) in rats taking into account sex-dependent effects and chronic treatment with aripiprazole (30days), an atypical antipsychotic acting as a partial agonist on dopaminergic receptors. RESULTS: We found the sex of the animal to have a highly significant effect in all regions of interest, with females showing lower blood perfusion than males. However, both males and females treated prenatally with poly(I:C) showed enlargement of the lateral ventricles. Furthermore, we detected increased perfusion in the circle of Willis, hippocampus, and sensorimotor cortex, which was not influenced by chronic atypical antipsychotic aripiprazole treatment in male poly(I:C) rats. CONCLUSION: We hypothesize that perfusion alterations may be caused by the hyperdopaminergic activity in the poly(I:C) model, and the absence of aripiprazole effect on perfusion in brain regions related to schizophrenia may be due to its partial agonistic mechanism.
BACKGROUND AND PURPOSE: One of the hallmarks of schizophrenia is altered brain structure, potentially due to antipsychotic treatment, the disorder itself or both. It was proposed that functional changes may precede the structural ones. In order to understand and potentially prevent this unwanted process, brain function assessment should be validated as a diagnostic tool. METHODS: We used Arterial Spin Labelling MRI technique for the evaluation of brain perfusion in several brain regions in a neurodevelopmental poly(I:C) model of schizophrenia (8mg/kg on a gestational day 15) in rats taking into account sex-dependent effects and chronic treatment with aripiprazole (30days), an atypical antipsychotic acting as a partial agonist on dopaminergic receptors. RESULTS: We found the sex of the animal to have a highly significant effect in all regions of interest, with females showing lower blood perfusion than males. However, both males and females treated prenatally with poly(I:C) showed enlargement of the lateral ventricles. Furthermore, we detected increased perfusion in the circle of Willis, hippocampus, and sensorimotor cortex, which was not influenced by chronic atypical antipsychoticaripiprazole treatment in male poly(I:C) rats. CONCLUSION: We hypothesize that perfusion alterations may be caused by the hyperdopaminergic activity in the poly(I:C) model, and the absence of aripiprazole effect on perfusion in brain regions related to schizophrenia may be due to its partial agonistic mechanism.
Authors: Roza M Vlasova; Ana-Maria Iosif; Amy M Ryan; Lucy H Funk; Takeshi Murai; Shuai Chen; Tyler A Lesh; Douglas J Rowland; Jeffrey Bennett; Casey E Hogrefe; Richard J Maddock; Michael J Gandal; Daniel H Geschwind; Cynthia M Schumann; Judy Van de Water; A Kimberley McAllister; Cameron S Carter; Martin A Styner; David G Amaral; Melissa D Bauman Journal: J Neurosci Date: 2021-10-04 Impact factor: 6.709
Authors: Tobias C Wood; Michelle E Edye; Michael K Harte; Joanna C Neill; Eric P Prinssen; Anthony C Vernon Journal: Brain Neurosci Adv Date: 2019-11-04