Main author: Fatich Mechmet
Institution or Company: Department of Anatomy, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland
Co-Authors, Institution or Company:
Eiríkur Steingrímsson, Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland. Pétur Henry Petersen, Department of Anatomy, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland.
Introduction: Microphthalmia-associated transcription factor (Mitf) encodes a member of the Myc supergene family of basic helix-loop-helix zipper (bHLH-Zip) transcription factors. Mitf is a master regulator of melanocyte cell fate and function as well as a melanoma risk factor and has a distinct expression in projection neurons, mitral and tufted (M/T) cells, of the olfactory bulb (OB). The OB is the first brain structure that mediates olfactory information processing in the central nervous system and has well-defined and multi-layered neuronal subtypes. Recently, our group has established that the MITF protein plays a critical role in homeostatic intrinsic plasticity in OB neurons through the regulation of the expression of key potassium channel subunits. In young Mitf null mice the expression of the potassium channel is reduced resulting in hyperactive projection neurons. Regulation of neuronal activity is the major determinant of neuroplasticity; importantly, the loss of neuronal activity homeostasis appears to be a characteristic of most neurodegenerative diseases.
Methods: Here, we focus on changes that occur in neuronal morphology and number of projection neurons in aged Mitf null mice, using Golgi-COX method, immunohistochemistry, transcriptomic data, and a behavioural test (hidden food assay).
Results: Primary results indicate that aged Mitf null mice have defective olfaction, changes in the number of projection neurons and their structure, and large-scale changes in gene expression in the OB.
Conclusion: Our data suggest that long-term hyperactivity might have detrimental effects on the mouse OB due to alterations in neuronal activity regulation.