Role of KCNQ1 Gene in Mental and Metabolic Disturbances Associated with Insulin Signalling Dysregulation

Metabolic imbalances (such as diabetes, obesity, and metabolic syndrome) significantly increase the risk of cognitive disturbances, including Alzheimer’s disease, dementia, obsessive compulsive disorders, autism spectrum disorders, and attention deficit hyperactivity disorders. In this context, KCNQ1, a voltage-gated potassium channel, is a key connecting metabolism and cognition. Different scholars, including preclinical and clinical scientists, and geneticists, have identified a potential contribution of the KCNQ1 gene as a key mediator of insulin signalling pathways. My project aimed to identify mechanisms involving peripheral and central dysregulation of insulin signalling, assessing KCNQ1-related effects in the brain. To achieve this aim, I conducted behavioural, physiological, and metabolic tests in a conditional kcnq1 knockout mouse model. In those experimental subjects, kcnq1 is downregulated in a time- (during adolescence and adulthood) and spatial- (only in the brain) specific manner. My findings showed that kcnq1 deletion in the brain significantly impairs cognitive abilities in rodents; specifically, executive functions.My experimental findings disclose innovative potential therapeutic avenues revolving around KCNQ1 as a candidate target to mitigate insulin-mediated cognitive decline.