Fig. 6: The PC core protein IFT20 is required to mediate the rejuvenating effects of OCN on age-related memory deficits.
From: A primary cilia–autophagy axis in hippocampal neurons is essential to maintain cognitive resilience
a,b, Stereotactic injections with AAV-eSYN-shRNA-scramble-mir or AAV-eSYN-shRNA-Ift20-mir were performed on 3-month-old or 16-month-old mice before 28-d peripheral infusion with vehicle or OCN. In a, western blot analysis and quantification of LC3B-I/II and SQSTM1/p62 accumulation from hippocampi. In b, discrimination and preference indexes of the NOR test. The NOR test was performed in two independent experiments for each group of mice. Data are expressed as mean ± s.e.m., and P values were determined by one-tailed Student’s t-test compared to control groups (a) and by one-way ANOVA with Tukey’s multiple comparison test (b). c, Graph theory and network analysis to determine elements within the network. Nodes represent pathways or protein expression. By analyzing connections between nodes, we can identify central and peripheral nodes within a cluster (or the entire network). Central nodes are associated with the core functionality of the cluster, whereas nodes positioned at the periphery of the cluster are associated with the nodes contributing to communication coordination. d, Pathway interaction graph based on the analysis of differentially expressed proteins from our proteomic data with KEGG databases, using a graph theory approach. Pathways were ordered based on their importance within the overall network using three parameters as detailed in the main text. Pathways with a combined coefficient greater than 0.35 are listed. *: pathways closely associated with those of zone A; **: pathways belonging to zone A. e, Graph illustrating the link between PC and autophagy-related pathways. A direct link could come through a KIF3A–PRKACA interaction. f, Identification of coordinated expression patterns within pathways in d. Only proteins with a significant impact within the network connectivity were taken into account. Rap1, Ras and PI3K/Akt pathways were the closest ones to localize near the identified zone A. Within the zone A, the most representative expressed proteins were involved in the cAMP signaling pathway. g, Histogram showing the strength of coordinated expression pattern in differentially expressed proteins from the ranked signaling pathway list in d. Mo, month-old.
