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Mechmet, F.

Publications and source records attributed to Mechmet, F..

2 recordsLinked to original sources

MITF regulates gene expression in middle tufted neurons and other projection neurons of the olfactory bulb

The microphthalmia-associated transcription factor (MITF) is a master transcription factor in melanocytes and plays equally important roles in mast cells. It is required for the generation, differentiation, and function of these cell types in vertebrates. Mitf is also expressed in the projection neurons of the olfactory bulb (OB), the mitral and tufted (M/T) cells. Loss of Mitf leads to neuronal hyperactivity in primary M/T cells but the general function of Mitf in neurons is unknown. Here, we identify putative MITF target genes in M/T cells, which show limited overlap with known targets in other cell types. These genes can be divided into two groups, those likely to inhibit neuronal activity and genes expressed specifically in a subclass of tufted cells, the middle tufted cells (mTCs). The mTCs are reduced in number in the Mitf mutant OB, suggesting a role for Mitf in the generation or survival of the mTCs and/or their function. Significance statementIdentifying MITF target genes in the OB offers insights into its role in olfaction and the regulation of neuronal activity as well as uncovering its role in mTCs. MITF may play a role in various other processes in neurons.

neuroscience↗

Reduction in olfactory ability in aging Mitf mutant mice without neurodegeneration

Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction, where the olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. Decline in olfaction is also associated with early symptoms of neurodegenerative diseases including Alzheimers disease (AD) and Parkinsons disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB - the mitral and tufted (M/T) cells. Primary M/T cells from Mitf mutant mice show hyperactivity, potentially attributed to reduced expression of a key potassium channel subunit, Kcnd3/Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence of Mitf has degenerative effects during aging. Aged Mitf mutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OB suggests that during aging compensatory mechanisms lead to stabilization. Significance statementThis study highlights the age-related decline in olfaction and elucidates compensatory mechanisms mediated by potassium channels. These findings improve our comprehension of the processes underlying age-related changes in olfaction.

neuroscience↗