A highly reproducible mice model of chronic kidney disease: Evidences of behavioural abnormalities and blood-brain barrier disruption

• Published in: Life sciences (1973) 2016-09, Vol.161, p.27-36
• Main Authors: Mazumder, Muhammed Khairujjaman, Giri, Anirudha, Kumar, Sanjeev, Borah, Anupom
• Format: Article
• Language: English
• Subjects: Adenine - administration & dosage; Animals; Behavior, Animal; Blood-Brain Barrier; Brain - pathology; Chronic renal failure; Creatinine - blood; Diet; Disease Models, Animal; End-stage renal disease; Evans blue dye; Female; Fibrosis - etiology; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - physiopathology; Kidney Failure, Chronic - psychology; Mice; Organ Size; Picro-Sirius red staining; Psycho-motor behaviour; Renal fibrosis; Reproducibility of Results; Urea - blood
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2016.07.020

In the present study, a novel mice model of chronic kidney disease (CKD) was developed, and psycho-motor behavioural abnormalities, blood-brain barrier (BBB) integrity and brain histology were studied. Swiss albino female mice were given high adenine diet (0.3% w/w mixed with feed) for 4weeks. Serum urea and creatinine levels and renal histological studies were performed to validate the model. Psycho-motor behavioural abnormalities and neurological severity were studied. BBB integrity was assessed using Evans blue extravasation method. Nissl staining was performed to see possible morphological aberrations in brain. There was a significant increase in serum urea and creatinine levels in mice given high adenine diet, and the mice had abnormal kidney morphology. Deposition of adenine and 2,8-dihydroxyadenine crystals, and increased collagen deposits in the renal tissues were found, which validate induction of CKD in the mice. Motor behavioural abnormalities, depression-like and anxiolytic behaviour and increase in neurological severity were prevalent in mice with CKD. Evans Blue dye extravasation was found to occur in the brain, which signifies disruption of BBB. However, Nissl staining did not reveal any morphological aberration in brain tissue. The present study puts forward a highly reproducible mice model of CKD validated with serum parameters and renal histopathological changes. The mice showed psycho-motor behavioural abnormalities and BBB disruption. It is a convenient model to study the disease pathology, and understanding the associated disorders, and their therapeutic interventions.