Abstract
The primary cilia of forebrain neurons assemble around birth and become enriched with neuromodulatory receptors. Our understanding of the permanence of these structures and their associated signaling pathways in the aging brain is poor, but they are worthy of investigation because disruptions in neuronal cilia signaling have been implicated in changes in learning and memory, depression-like symptoms, and sleep anomalies. Here, we asked whether neurons in aged forebrain retain primary cilia and whether the staining characteristics of aged cilia for type 3 adenylyl cyclase (ACIII), somatostatin receptor 3 (SSTR3), and pericentrin resemble those of cilia in younger forebrain. To test this, we analyzed immunostained sections of forebrain tissues taken from young and aged male Fischer 344 (F344) and F344 × Brown Norway (F344 × BN) rats. Analyses of ACIII and SSTR3 in young and aged cortices of both strains of rats revealed that the staining patterns in the neocortex and hippocampus were comparable. Virtually every NeuN positive cell examined possessed an ACIII positive cilium. The lengths of ACIII positive cilia in neocortex were similar between young and aged for both strains, whereas in F344 × BN hippocampus, the cilia lengths increased with age in CA1 and CA3, but not in dentate gyrus (DG). Additionally, the percentages of ACIII positive cilia that were also SSTR3 positive did not differ between young and aged tissues in either strain. We also found that pericentrin, a protein that localizes to the basal bodies of neuronal cilia and functions in primary cilia assembly, persisted in aged cortical neurons of both rat strains. Collectively, our data show that neurons in aged rat forebrain possess primary cilia and that these cilia, like those present in younger brain, continue to localize ACIII, SSTR3, and pericentrin. Further studies will be required to determine if the function and signaling pathways regulated by cilia are similar in aged compared to young brain.
Highlights
Primary cilia are non-motile, microtubule-based organelles that extend from nearly every cell type in the body including neurons
Given the evidence linking primary cilia and brain function, and the complex mechanisms required to build and maintain a cilium, in this study we explored whether neurons in the forebrains of aged rats are ciliated and whether these cilia retain adenylyl cyclase subtype III (ACIII) and somatostatin receptor subtype 3 (SSTR3) immunostaining profiles that resemble those observed in the forebrains of younger rats
The ACIII+ cilia in CA1 and CA3 regions of hippocampus were significantly longer in aged compared to young brains (Figure 1G); this difference was not noted in comparison of the cilia within the dentate gyrus (DG)
Summary
Primary cilia are non-motile, microtubule-based organelles that extend from nearly every cell type in the body including neurons. Similar results have been obtained in recent studies of adult born dentate granule neurons In these studies, ablation of ACIII+ cilia by expressing a dominant negative form of Kif3a in these granule cells disrupted their ability to develop dendrites and integrate into the adult brain (Kumamoto et al, 2012). Evidence that primary cilia dysfunction or loss alters neuronal and brain function comes from studies in which knockout of either ACIII or SSTR3 disrupts synaptic plasticity, behavior, and novel object recognition memory in mice (Einstein et al, 2010; Wang et al, 2011; Chen et al, 2016). Many ciliopathy patients present with cognitive impairments and other symptoms associated with CNS dysfunction (Valente et al, 2014; Guo et al, 2015)
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