Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021
Erindi/veggspjald / Talk/poster E73
Höfundar / Authors: Fatich Mechmet (1), Eiríkur Steingrímsson (2), Pétur Henry Petersen (1)
Starfsvettvangur / Affiliations: 1. Department of Anatomy, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, 2. Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland
Kynnir / Presenter: Fatich Mechmet
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 functions 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. It has been shown that both in humans and animals there are age-related changes in the OB. However, the molecular and cellular mechanisms underlying olfactory dysfunction are often unknown. In addition, in humans the decrease in the olfactory ability is an early symptom of neurodegenerative diseases such as Alzheimer´s disease (AD) and Parkinson´s disease (PD). Studying the OB of aging mice using molecular tools and omic technologies together with behavioral experiments may contribute to our understanding of the cause of these deficits in the aging olfactory system. 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 potassium channels 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. In this study we provide an overview of changes that occur in neuronal and glia morphology , using Golgi-COX method, immunohistochemistry, electron microscopy, transcriptomic data and behavioral tests. Results show that aged Mitf null mice have defective olfaction and large-scale changes in gene expression, with no signs of inflammation or neurodegeneration in the OB. Our data suggest that long-term hyperactivity has detrimental effects on olfaction and in turn might also contribute age-related deficits in the OB due to alterations in neuronal activity regulation.