Abstract: SA-PO0295
Impaired Brain Tissue Clearance in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Fukasawa, Motoaki, Fujita Health University, Toyoake, Aichi, Japan
- Nagao, Shizuko, Fujita Health University, Toyoake, Aichi, Japan
- Takahashi, Kazuo, Fujita Health University, Toyoake, Aichi, Japan
Background
Patients with diabetic nephropathy (DN) occasionally exhibit functional changes, such as increased irritability and an elevated risk of dementia. These clinical findings suggest that renal impairment might induce alterations within the brain. However, the specific mechanisms linking renal dysfunction to brain changes remain unclear. In this study, we investigated the effects of DN on the intracerebral environment by focusing on cerebrospinal fluid (CSF) flow dynamics and parenchymal alterations in the brain.
Methods
DN model rats were established by performing a left nephrectomy and providing 0.3% saline as drinking water in diabetic SDT Fatty/Jcl rats. To analyze CSF dynamics, a dialysis probe was inserted into the lateral ventricle, and FITC-labeled dextran (70 kDa) was administered intravenously via the tail vein. CSF dialysate samples were then collected, and fluorescence intensity was measured. Additionally, fluorescently labeled β-amyloid was microinjected into the striatum, and one hour later, brain sections were analyzed using fluorescence microscopy to assess the extent of dye diffusion and cellular uptake. Gene expression analysis of the choroid plexus was conducted to quantify the expression of permeability-associated markers, such as aquaporin-4 (AQP4) and PV1.
Results
Upon intravenous administration of FITC-dextran, diabetic model rats exhibited a transient increase in CSF fluorescence intensity; this effect was absent in DN rats. FITC accumulation in the choroid plexus epithelium was significantly reduced in DN rats compared to diabetic controls. Similarly, when β-amyloid was injected into the striatum, DN rats displayed greater diffusion and cellular uptake of the fluorophore, indicating impaired parenchymal clearance. Gene expression analysis revealed lower levels of AQP4 and PV1 expression in DN rats, highlighting reduced CSF transport and permeability.
Conclusion
Our findings demonstrate that DN leads to decreased choroid plexus permeability, impaired glymphatic function, and reduced brain tissue clearance. These alterations may significantly impact the brain’s microenvironment, potentially contributing to functional deficits, including cognitive impairment and dementia observed in DN patients.
Funding
- Government Support – Non-U.S.