Diabetic Encephalopathy in a Preclinical Experimental Model of Type 1 Diabetes Mellitus: Observations in Adult Female Rat.
Eva FalvoSilvia GiattiSilvia DiviccaroLucia CioffiMonika HerianPaola BrivioFrancesca CalabreseDonatella CarusoRoberto Cosimo MelcangiPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- cognitive impairment
- oxidative stress
- cerebral ischemia
- working memory
- subarachnoid hemorrhage
- glycemic control
- type diabetes
- end stage renal disease
- wound healing
- early onset
- traumatic brain injury
- brain injury
- ischemia reperfusion injury
- dna damage
- blood brain barrier
- diabetic rats
- chronic kidney disease
- ejection fraction
- lipopolysaccharide induced
- newly diagnosed
- functional connectivity
- induced apoptosis
- lps induced
- peritoneal dialysis
- cognitive decline
- mesenchymal stem cells
- mild cognitive impairment
- white matter
- ms ms
- prognostic factors
- stem cells
- skeletal muscle
- prefrontal cortex
- estrogen receptor
- endoplasmic reticulum stress
- signaling pathway