Morphological and mitochondrial changes in murine choroid plexus epithelial cells during healthy aging

Choroid plexuses (ChPs) are intraventricular structures mainly composed by specialized epithelial cells interconnected by tight junctions establishing the blood-cerebrospinal fluid (CSF) barrier. ChPs are essential to produce CSF and transport solutes from and into the brain. Changes in ChP morphology and function have been correlated to neurodegenerative disorders. Using electron microscopy, two-photon microscopy and biochemistry, we have investigated ChP epithelial cells during healthy aging, starting from young adult to two-years old mice. We identified distinct morpho-functional modifications in ChP epithelial cells in mice aged 8-12 months, which mostly remained stable up to two years. These changes include flattening of the epithelium, reduction of microvilli length, enlargement of basolateral membrane invaginations and augmentation of interrupted tight junctions. We also found a decrease in mitochondria density together with elongation of mitochondria in older mice. Two-photon imaging of whole ChP living explants revealed that morphological rearrangements of mitochondria were accompanied by increased superoxide levels, decreased membrane potential and decreased mitochondrial motility in aged mice, suggesting possible mitochondrial oxidative damage and impaired ability to synthetize ATP at baseline. Interestingly, most of the age-related changes were not accompanied by modification of protein and/or gene expression levels and aged mitochondria effectively responded to acute pharmacological stressful stimuli, raising the possibility that the morphological remodeling observed in mitochondria may represent an adaptive mechanism engaged by ChP epithelial cells to endure stressful events. Our study suggests a long-term progression of multiple morpho-functional features of the mouse choroid plexus epithelium during lifetime.