Relationship between p62 and learning behavior in male and female mice deficient in hippocampal folliculin

Alzheimer’s disease is a degenerative disease characterized by loss of memory, loss of cognitive function, and functional impairment with associated neuropsychological symptoms. Sequestosome 1 (referred to henceforth as p62) is a ubiquitin-binding scaffold protein that transports ubiquitinated targets to autophagosomes for degradation. Folliculin (FLCN) is a protein that affects diverse signaling pathways involving lysosome biogenesis, a cellular process increasingly relevant to neurodegenerative diseases like Alzheimer’s disease. p62 was among several proteins that had not been studied regarding FLCN manipulation in the dorsal hippocampus between sexes in young C57BL6/J wild-type mice. We hypothesized that if FLCN and p62 are functionally connected, then reducing FLCN may have downstream effects on p62 protein levels, an effect we examined in both female and male mice. To this end, we used western blots to measure p62 levels in the samples from a previous study that used shRNA against FLCN in female and male mice (N = 28, 13 males, 15 females) in the dorsal hippocampus. Our p62 data was analyzed with a two-way analysis of variation (ANOVA), sex (male, female) x folliculin (control, shRNA), to determine the effects of the independent variables on p62 expression. We found that p62 regressed with folliculin expression levels. Other studies indicate that p62 impacts memory function; however, our results show there is no evidence of a functional connection between FLCN and p62 in young wild-type mice. Our work may therefore impact future p62 research and does not preclude the possibility that p62 may affect cognitive functioning in diseased and/or aged models.