Chronic kidney disease is accompanied by dysregulation of depression biomarkers in the rat hippocampus
Description
Clinical reports indicate a bidirectional relationship between chronic systemic disease and mental health conditions. Chronic kidney disease (CKD), a debilitating progressive illness, has been linked to changes in the limbic brain areas and development of anxiety and depression. We recently showed that severe CKD in rats is accompanied by a depressive/anxiogenic behavioral phenotype; however, the underlying neurophysiological mechanisms remain elusive. Thus, here we aimed to identify transcriptomic biomarkers in the hippocampus, a limbic brain involved in stress responses and mood regulation, by comparing differentially expressed genes (DEGs) in the CKD rat model with DEGs previously found in postmortem human depressed brains. Genome-wide RNA-seq analysis was used to examine the hippocampal transcriptomic profile from male rats exposed to a 21-day adenine diet (AD) in combination with unilateral nephrectomy (i.e., severe CKD model). Gene expression profile of postmortem hippocampus subregions, dentate gyrus (DG) and CA1, from human subjects diagnosed with MDD (n=15) was assessed by 48K HEEBO whole genome microarrays (Duric et al., 2010). Further qPCR validation revealed dysregulation of “overlapping” genes in the hippocampus of CKD animals involved in 1) neurotrophic signaling (e.g., BDNF, MKP-1, IGF-2, galanin), 2) blood-brain barrier (BBB) integrity (e.g., VEGF, FLT-1, MMP9, NOTCH4), and 3) neuroinflammation and oxidative stress (e.g., Aurk-B, IMMP2L). These findings suggest that decreased kidney function in our rat CKD model evokes brain pathologies similar to human depression, and points to neural mechanisms that could be targeted for development of improved treatments of mental health comorbidities associated with kidney disease.
Citation Information
Ballweber, Sydney; Bane, Rachel; Kulkarni, Siddharth; Chapman, James; Di Sole, Francesca; Babich, Victor; and Duric, Vanja, "Chronic kidney disease is accompanied by dysregulation of depression biomarkers in the rat hippocampus" (2026). Office of Research DMU Research Symposium. 69.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/69
Chronic kidney disease is accompanied by dysregulation of depression biomarkers in the rat hippocampus
Clinical reports indicate a bidirectional relationship between chronic systemic disease and mental health conditions. Chronic kidney disease (CKD), a debilitating progressive illness, has been linked to changes in the limbic brain areas and development of anxiety and depression. We recently showed that severe CKD in rats is accompanied by a depressive/anxiogenic behavioral phenotype; however, the underlying neurophysiological mechanisms remain elusive. Thus, here we aimed to identify transcriptomic biomarkers in the hippocampus, a limbic brain involved in stress responses and mood regulation, by comparing differentially expressed genes (DEGs) in the CKD rat model with DEGs previously found in postmortem human depressed brains. Genome-wide RNA-seq analysis was used to examine the hippocampal transcriptomic profile from male rats exposed to a 21-day adenine diet (AD) in combination with unilateral nephrectomy (i.e., severe CKD model). Gene expression profile of postmortem hippocampus subregions, dentate gyrus (DG) and CA1, from human subjects diagnosed with MDD (n=15) was assessed by 48K HEEBO whole genome microarrays (Duric et al., 2010). Further qPCR validation revealed dysregulation of “overlapping” genes in the hippocampus of CKD animals involved in 1) neurotrophic signaling (e.g., BDNF, MKP-1, IGF-2, galanin), 2) blood-brain barrier (BBB) integrity (e.g., VEGF, FLT-1, MMP9, NOTCH4), and 3) neuroinflammation and oxidative stress (e.g., Aurk-B, IMMP2L). These findings suggest that decreased kidney function in our rat CKD model evokes brain pathologies similar to human depression, and points to neural mechanisms that could be targeted for development of improved treatments of mental health comorbidities associated with kidney disease.
