Nuclear and Cytoplasmic Mouse ID Associated 1 (MIDA1) Protein Varies in Neurons and Astrocytes Across the Different...

Nuclear Mouse ID Associated 1 (MIDA1), also known as Hsp40/DNAJC2 and ZRF1, plays a key role in the establishment of neural progenitors in the brain. In the cytoplasm, MIDA1 ensures proper protein folding, which, if disrupted, can lead to protein misfolding and ultimately neurodegeneration. Thus, MIDA1 is crucial for maintaining brain cell homeostasis. However, it remains unclear whether neurons and astrocytes express MIDA1 equally, whether the distribution of MIDA1 between the nucleus and cytoplasm differs, and if this difference changes with age. Therefore, we evaluated MIDA1 content and distribution in neurons and astrocytes of the CA1, CA3, and dentate gyrus (DG) in 3- and 12-month-old mice. The results indicated that, relative to the nucleus, cytoplasmic MIDA1 content is higher in neurons and astrocytes at both ages. An overall reduction of MIDA1 in the nucleus of neurons was noted with age, while the three-month-old mice displayed increased cytoplasmic MIDA1. In contrast, astrocytes exhibited similar levels of MIDA1 in the nucleus across the hippocampal regions analyzed. However, astrocytes from the CA1 and CA3 regions in the 12-month-old group showed increased cytoplasmic MIDA1 content. Lastly, a comparison of MIDA1 immunofluorescence between neurons and astrocytes revealed that astrocytes exhibit lower nuclear MIDA1 levels at both ages. Notably, at 12 months, cytoplasmic MIDA1 levels were higher in astrocytes than in neurons. Given that MIDA1 function depends on its subcellular location, our results suggest that MIDA1 undergoes more dynamic changes in the cytoplasm across different hippocampal areas, becoming more pronounced in astrocytes at 12 months. Thus, the chaperone role of MIDA1 may be particularly crucial as astrocytes and neurons age, coinciding with the appearance of age-related cognitive deficits detected in the novel object recognition test.