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Focal cortical dysplasia (FCD) type 2 is a congenital brain malformation characterized by atypical organization of neurons in the cerebral cortex, frequently leading to epilepsy that is challenging to manage. A collaborative research initiative involving the University Hospital Bonn (UKB), the University of Bonn, and the German Center for Neurodegenerative Diseases (DZNE) has revealed significant alterations in the dopaminergic system in FCD type 2. These findings have been published in the medical journal Brain.
Dopamine, a key neurotransmitter, plays a vital role in various cognitive processes such as attention and learning, as well as in modulating the excitability of neuronal circuits. Prior to this study, the specific effects of FCD on the dopamine system had not been extensively examined. The recent research indicates that the dopaminergic inputs in the regions affected by FCD are not functioning normally. Increased levels of specific dopamine receptors were noted in both human brain tissue and a corresponding mouse model.
Evidence of disturbed modulation in the developing cortex
“Our findings imply that the dopaminergic system is disrupted in individuals with FCD type 2,” states Norisa Meli, a PhD candidate at the University of Bonn’s Institute for Reconstructive Neurobiology at the UKB, and the study’s lead author. “Notably, we found a significant rise in dopaminergic receptor expression in neurons implicated in the disease’s progression.”
These observed changes may contribute to the onset of epileptic seizures and help elucidate why patients also report experiencing difficulties with concentration or fluctuations in mood.
“Dopamine influences the excitability and development of neuronal networks in the cortex,” highlights Prof. Sandra Blaess, a Neurodevelopment Professor at UKB and a member of the TRA ‘Life & Health’ at the University of Bonn. “Our findings suggest that this modulation is disrupted in FCD type 2, a phenomenon that has received little attention in previous research.”
Prof. Albert Becker, who leads the Institute for Cellular Neuroscience II at UKB and is part of the TRA ‘Life & Health’, notes, “These discoveries enhance our understanding of the complex neuropathology associated with dysplasias, providing essential insights for potential new therapeutic strategies that might extend beyond merely controlling seizures.”
The study integrates detailed molecular analyses of human tissue with a preclinical mouse model that mirrors the genetic alterations seen in FCD type 2. The researchers aspire that this work will pave the way for more targeted and effective therapies in the future. Funding for the study was provided by the German Research Foundation, the BONFOR initiative of the Medical Faculty of the University of Bonn, and the iBehave project (part of an initiative by the Ministry of Culture and Science of North Rhine-Westphalia). Additionally, support came from the Epilepsy Surgery Biobank of the Medical Faculty of the University of Bonn and the Open Access funding of the University of Bonn.
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