Reduction in the olfactory ability in aging Mitf mutant mice without evidence of neurodegeneration

Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction. The olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. A decline in olfaction is also associated with early symptoms of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's 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 <i>Mitf</i> mutant mice show hyperactivity, potentially attributed to the reduced expression of a key potassium channel subunit, <i>Kcnd3</i>/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 <i>Mitf</i> causes degenerative effects during aging. Aged <i>Mitf</i> mutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OBs of aged <i>Mitf</i> ^{<i>mi-vga9/mi-vga9</i>} mice suggests that during aging, compensatory mechanisms lead to stabilization.