Investigating the Role of the Mitochondrial Calcium Uniporter in Inflammatory Neurodegeneration
Publish place: Third International Nervous System Inflammatory Conference and Third Student Neuroscience Festival
Publish Year: 1398
نوع سند: مقاله کنفرانسی
زبان: English
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شناسه ملی سند علمی:
NIMED03_043
تاریخ نمایه سازی: 7 آبان 1398
Abstract:
The Mitochondrial Calcium Uniporter (MCU) regulates Ca2+-influx into mitochondria. In case of neurological disease, an excessive Ca2+ influx (Caoverload) plays a major role in post-lesional neuronal degeneration and death. Materials and Methods: To further elucidate the role of the MCU in CNS pathophysiology, we generated neuron-specific MCU knockout mice in order to study them in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). We hypothesize that neuronal damage can be reduced by inactivatingthe MCU, offering therapeutic opportunities. We crossbred neuron-specific cre (NexCre) transgenic and homozygous loxP floxed mice. After one generation we obtained hemizygous, neuron-specific Cre (NexCre) mice which were heterozygous for the floxed MCUgene. These animals were crossbred with homozygous, loxP floxed MCU gene mice to obtain an F2 generation with a homozygous knockout for MCU in Nexexpressing cells (neurons). Results: Genotyping confirmed the successful breeding of such homozygous floxed animals with Cre expression. The transgenic mice are healthy and do not show any conspicuous differences as compared to their non-transgeniclittermates. Conclusion: We will use these mice, induce EAE and compare the disease courses of knockout mice with non-transgenic controls. Furthermore, we will analyze Ca2+-dependent mechanisms of neuronal degeneration by use of histopathological and live imaging techniques.
Authors
Laura Bierhansl
Clinic for Neurology with Institute of Translational Neurology, University Clinic Muenster, Muenster, Germany
Petra Hundehege
Clinic for Neurology with Institute of Translational Neurology, University Clinic Muenster, Muenster, Germany
Iska Loesmann
Clinic for Neurology with Institute of Translational Neurology, University Clinic Muenster, Muenster, Germany
Petra Henrich-Noack
Clinic for Neurology with Institute of Translational Neurology, University Clinic Muenster, Muenster, Germany