Investigating the Neuroprotective Impacts of Chenodeoxycholic Acid in STZ-Induced Diabetic Neuropathy and Cognitive Impairment in BALB/c Mice

Abstract

Diabetic neuropathy and cognitive impairment are common complications of diabetes, significantly affecting the lives of millions of people. Finding effective treatments for these issues remains a critical challenge. In this study, we investigated whether chenodeoxycholic acid, a naturally occurring bile acid known for its neuroprotective properties, could help alleviate these complications. We utilized a mouse model of diabetes induced by streptozotocin. The mice were categorized into three groups; a healthy control, a diabetic group and a diabetic group that receive treatment with CDCA. The diabetic mice displayed typical signs of nerve pain, anxiety-like behaviour, and memory problems. However, those treated with CDCA showed remarkable improvements in all these areas. They experienced less pain in the hot plate analgesia, exhibited reduced anxiety levels in the open field test, and demonstrated better memory and cognitive function in the test of Y-maze. Beyond behaviour, CDCA also had profound effects on the brain. It preserves the structure of neurons in critical areas like the hippocampus and cortex, which are often affected by diabetic neuropathy. At a molecular level, CDCA may reduce inflammation by decreasing nuclear factor kappa B levels, a key marker of inflammation and cell damage. The brain-derived neurotrophic factor is also increased, a protein essential for nerve growth and repair in the brain, suggesting that CDCA supports the brain’s natural ability to heal. These results provide a promising glimpse into the potential of CDCA as a treatment for diabetes-related nerve and cognitive problems. While more research is needed, the ability of CDCA to protect neurons, reduce inflammation, and improve cognitive and behavioural outcomes makes it a promising drug for future therapies aimed at improving the lives of people with diabetes.