Chronic kidney disease (CKD) is a global health issue, often associated with cognitive and behavioural disturbances. The cytochrome P450 enzyme CYP2C19 has previously been associated with neurobehavioural changes. Humanised transgenic CYP2C19 mice show emotional changes, and abnormalities in locomotion and in brain regions involved in memory and stress response. This study aimed to investigate whether cognitive impairments in CYP2C19 transgenic mice are related to impaired renal function or structure. Adult male and female wild-type and CYP2C19 mice (total N = 41) were included in the study. Behavioural phenotyping was performed by examining short-term memory in Novel Object Recognition Test (NORT) and social interaction in Social Recognition Test (SRT). After 24 h, urine was collected, animals were sacrificed, and blood samples and kidneys were collected and used for biochemical assays and histological assessment. NORT and SRT revealed cognitive deficits and possible social anxiety in CYP2C19 mice compared to wild-type controls, as no difference was observed in time CYP2C19 mice spent interacting with novel objects or unfamiliar animals. Biochemical analysis showed no significant differences in total protein, albumin, urea, creatinine and uric acid between experimental groups. Histological evaluation confirmed that there was no structural kidney damage in CYP2C19 mice. Our findings indicate that in CYP2C19 mice, cognitive and behavioural changes described here are independent of renal dysfunction. Therefore, CYP2C19 mouse model represents a valuable tool to study cognitive impairment without concomitant kidney disease and could serve as a suitable control in studies investigating the interplay between cognitive decline and CKD.
Keywords: CYP2C19 transgenic mouse model; Chronic kidney disease (CKD); Kidney; Novel object recognition test (NORT); Social recognition test (SRT).
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