Exploration of the Cerebral Dysfunctions Induced by Arterial Rigidity and/or the Overexpression of TGFβ in a Mouse Model
Introduction: Alzhemer’s disease (AD) and vascular dementia (VaD) is multifaceted with multiple cerebrovascular deficits and not limited to the amyloidβ (Aβ) pathology. Cerebral modifications include changes to vascular structure, which can be reproduced in transgenic mice overexpressing transforming growth factor β1 (TGFβ1), a cytokine found in increased quantities in brains of AD and VaD patients. The mouse model overexpressing TGFβ demonstrates a chronically compromised cerebral circulation, which may precipitate cognitive deficits if combined with other risk factors of cognitive decline, such as arterial rigidity. Objective: To determine whether arterial rigidity induced by calcification will provoke cerebrovascular dysfunctions in the TGFβ mouse and trigger cogitive deficits. Methodology: We tested whether arterial rigidity induced by calcification of the right carotid artery trigger deficits in memory and learning in mice overexpressing TGFβ1 and their wild type litermates in a set of young and a set of aged mice. Spatial memory and memory consolidation were studied via the Morris water maze (MWM) and novel object recognition (NOR) at 1-, 2- and 4-months followin surgery to induce arterial calcification. Results: No significant difference was observed between all groups in the NOR test or the spatial learning of MWM (1-, 2- and 4-months post-surgery). For the memory consolidation tests of the MWM, young TGF mice with calcification showed significance at 4-months post-surgery (p <0,05) while TGF mice without calcification failed to demonstrate cognitive deficits. Conclusion: These results suggest that arterial calcification and overexpression of TGFβ1 may act in a synergistic manner to trigger cognitive deficits. Therefore, these two pathways may constitute possible therapeutic targets for prevention of dementia. Keywords : TGFβ, arterial rigidity, dementia, Alzheimer, vascular dementia, Morris water maze, calcification, cerebral dysfunction, neurovascular unit
TGF beta behavioral testing Morris Water Maze Neurovascular coupling Alzheimer's disease Vascular dementia Dementia Neurovascular unit Mouse model Oxidative stress Gliosis Novel object recognition Cerebral dysfunction Calcification Arterial rigidity TGFβ Alzheimer