Chronic kidney disease is accompanied by dysregulation of hippocampal genes involved in blood-brain barrier integrity
Description
Kidney injury and inflammation have been linked to brain dysfunction and alterations in learning and memory, as well as development of anxiety and depression. Our previous findings showed that a chronic kidney disease (CKD) state is sufficient to produce enhanced behavioral emotionality (i.e., depressive/anxiogenic phenotype) based on behavioral testing using a severe model of CKD [i.e., male rats exposed to a 21-day adenine diet (AD) in combination with unilateral nephrectomy]. In this study, we aimed to identify novel limbic biomarkers and related cellular mechanisms that underlie development of comorbid depression during CKD. Genome-wide RNA-seq analysis was used to examine the transcriptomic profile of the hippocampus, a brain region that regulates mood and stress responses. RNA-seq bioinformatic analysis, followed by validation using qPCR, revealed dysregulation of hippocampal genes involved in blood-brain barrier (BBB) integrity, oxidative stress, and neuroprotection. Specifically, elevated levels of angiopoietin-2 (Angpt2), vascular endothelial growth factor (VEGF), and FMS-like tyrosine kinase (FLT1; also known as VEGF receptor 1), genes with functional roles in regulation of vascular homeostasis and BBB integrity, were significantly upregulated in the hippocampus of animals with severe CKD expressing increased behavioral emotionality. Increased levels of these biomarkers suggest that hippocampal BBB is compromised in the state of reduced kidney function, potentially representing a key pathophysiological factor that may contribute to development of behavioral deficits. These results point to mechanisms that may aid in the development of improved treatments and prevention strategies for management of mental health comorbidities associated with kidney disease.
Citation Information
Chapman, James; Kulkarni, Siddharth; Ballweber, Sydney; Bane, Rachel; Di Sole, Francesca; Babich, Victor; and Duric, Vanja, "Chronic kidney disease is accompanied by dysregulation of hippocampal genes involved in blood-brain barrier integrity" (2026). Office of Research DMU Research Symposium. 67.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/67
Chronic kidney disease is accompanied by dysregulation of hippocampal genes involved in blood-brain barrier integrity
Kidney injury and inflammation have been linked to brain dysfunction and alterations in learning and memory, as well as development of anxiety and depression. Our previous findings showed that a chronic kidney disease (CKD) state is sufficient to produce enhanced behavioral emotionality (i.e., depressive/anxiogenic phenotype) based on behavioral testing using a severe model of CKD [i.e., male rats exposed to a 21-day adenine diet (AD) in combination with unilateral nephrectomy]. In this study, we aimed to identify novel limbic biomarkers and related cellular mechanisms that underlie development of comorbid depression during CKD. Genome-wide RNA-seq analysis was used to examine the transcriptomic profile of the hippocampus, a brain region that regulates mood and stress responses. RNA-seq bioinformatic analysis, followed by validation using qPCR, revealed dysregulation of hippocampal genes involved in blood-brain barrier (BBB) integrity, oxidative stress, and neuroprotection. Specifically, elevated levels of angiopoietin-2 (Angpt2), vascular endothelial growth factor (VEGF), and FMS-like tyrosine kinase (FLT1; also known as VEGF receptor 1), genes with functional roles in regulation of vascular homeostasis and BBB integrity, were significantly upregulated in the hippocampus of animals with severe CKD expressing increased behavioral emotionality. Increased levels of these biomarkers suggest that hippocampal BBB is compromised in the state of reduced kidney function, potentially representing a key pathophysiological factor that may contribute to development of behavioral deficits. These results point to mechanisms that may aid in the development of improved treatments and prevention strategies for management of mental health comorbidities associated with kidney disease.
