Diabetic Encephalopathy in a Preclinical Experimental Model of Type 1 Diabetes Mellitus: Observations in Adult Female Rat

Patients affected by diabetes mellitus (DM) show diabetic encephalopathy with an increased risk of cognitive deficits, dementia and Alzheimer's disease, but the mechanisms are not fully explored. In the male animal models of DM, the development of cognitive impairment seems to be the result of the concomitance of different processes such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and aberrant synaptogenesis. However, even if diabetic encephalopathy shows some sex-dimorphic features, no observations in female rats have been so far reported on these aspects. Therefore, in an experimental model of type 1 DM (T1DM), we explored the impact of one month of pathology on memory abilities by the novel object recognition test and on neuroinflammation, synaptogenesis and mitochondrial functionality. Moreover, given that steroids are involved in memory and learning, we also analysed their levels and receptors. We reported that memory dysfunction can be associated with different features in the female hippocampus and cerebral cortex. Indeed, in the hippocampus, we observed aberrant synaptogenesis and neuroinflammation but not mitochondrial dysfunction and oxidative stress, possibly due to the results of locally increased levels of progesterone metabolites (i.e., dihydroprogesterone and allopregnanolone). These observations suggest specific brain-area effects of T1DM since different alterations are observed in the cerebral cortex.

Automated summary

Patients affected by diabetes mellitus (DM) have an increased risk of cognitive deficits, dementia, and Alzheimer's disease, but the mechanisms underlying diabetic encephalopathy are not fully understood. In this study, male animal models of DM showed cognitive impairment due to neuroinflammation, oxidative stress, mitochondrial dysfunction, and aberrant synaptogenesis. No observations in female rats have been reported on these aspects before, so the impact of type 1 DM on memory abilities, neuroinflammation, synaptogenesis, and mitochondrial functionality was explored in a female rat model. The findings suggest that T1DM has specific effects on different brain areas, with aberrant synaptogenesis and neuroinflammation observed in the hippocampus but not in the cerebral cortex.