title: A highly reproducible mice model of chronic kidney disease: Evidences of behavioural abnormalities and blood-brain barrier disruption.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Cellular & Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India.
authors: Muhammed Khairujjaman
authors: MK
authors: Mazumder
authors: Environmental Toxicology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India.
authors: Anirudha
authors: A
authors: Giri
authors: Microbial and Molecular Immunology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India.
authors: Sanjeev
authors: S
authors: Kumar
authors: Cellular & Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India. Electronic address: anupomborahh@gmail.com.
authors: Anupom
authors: A
authors: Borah
mesh_terms: D000225:Adenine / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D051379:Mice; D009929:Organ Size; D015203:Reproducibility of Results; D014508:Urea / Q000097:blood
chemical_list: D014508:Urea; D003404:Creatinine; D000225:Adenine
keywords: Chronic renal failure; End-stage renal disease; Evans blue dye; Picro-Sirius red staining; Psycho-motor behaviour; Renal fibrosis