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Authors & Affiliations
Ilenia Pinna, Carlotta Siddi, Simona Dedoni, Eleonora Cocco, Maria Scherma, Paola Fadda
Abstract
The renin-angiotensin system (RAS) is expressed in the brain and impacts physiological several activities. Dysregulation of the RAS may be associated with a wide spectrum of brain diseases defined by severe neuroinflammation, oxidative stress, and age-related pathophysiological processes. The CAG-hACE2 transgenic mice were designed to express the human angiotensin-converting enzyme 2 (hACE2) receptor, which is involved in the RAS. However, the relevance of ACE2 at the brain level remains unclear. The purpose of our research is to characterize CAG-hACE2 transgenic mice of both sexes, females and males, to determine if there are changes in the expression of the hACE2 transgene and its relationship to distinct activation of the RAS. Furthermore, considering the involvement of the RAS in neuropsychiatric and neurodegenerative disorders such as Multiple Sclerosis, Alzheimer's, and Parkinson's disease, this characterization may potentially be relevant to examine the role of ACE2 in neurological processes. The following behavioural tests have been used: Novel Object Recognition (NOR), Locomotor Activity, Marble Burying Test, and Elevated Plus Maze (EPM). Our preliminary results indicate that female CAG-hACE2 mice exhibit higher anxiety in the EPM test compared to their respective C57BL controls, while male CAG-hACE2 mice exhibit cognitive impairment in the NOR test. These preliminary studies need to be further investigated and accompanied by biochemical and molecular analysis. Investigations on this model will be useful to better understand the role of the RAS and the ACE2 enzyme in the CNS, as well as the possible consequences for neurodegenerative diseases that do not yet have definite therapies.