Anomalies du système olfactif et sa modulation en tant qu'approche thérapeutique dans les troubles cognitifs légers
Year: 2021
Type: dissertation
Abstract: Olfactory dysfunction and atrophy of olfactory brain regions are observed early in Mild Cognitive Impairment (MCI) and Alzheimer disease (AD). Numerous studies have shown neuroprotective effects in MCI/AD with treatment of docosahexaenoic acid (DHA), an omega-3 fatty acid. However, few studies have assessed DHA and its effects on olfactory system deficits. The objectives of our project were to determine if DHA treatment in a murine model of MCI improves cognitive and olfactory system deficits and establish if inflammation and/or excitotoxicity are early events in the olfactory regions in MCI. Our results show that APOE4 mice treated with the control diet showed recognition memory deficits, which was rescued by the DHA diet. In the olfactory behavior test, a significant reduction in habituation and discrimination abilities were observed in APOE4 mice on control diet, which was rescued with DHA. In the sucrose preference test, a measure of depression, APOE4 mice on the DHA diet had a significant decrease in preference for sucrose compared to WT mice. Early atrophy of the olfactory bulb (OB), olfactory tubercle, piriform cortex and amygdala was observed in APOE4 mice, showing no rescue with DHA. Moreover, a significant increase in the number of microglia was observed in the OB of APOE4 mice which was ameliorated with a DHA diet. In contrast, no rescue of increased NR2B positive cells in the APOE4 OB on the control diet was found in DHA-treated mice. In conclusion, the consumption of a diet rich in DHA may prevent the olfactory deficits and recognition memory decline observed in the APOE4 mice. The brain region atrophy observed in the APOE4 mice at early age could be due to caspase activation and/or alterations in neurogenesis. NR2B expression is altered in the APOE4 OB, which could lead to excitotoxicity and consequently, cell death. IBA-1 expression is upregulated in the OB of APOE4 mice at an early age, suggesting that there is microglia activation and a neuroinflammatory response, which is alleviated with DHA treatment.
Author: Martinez Gonzalez, Laura
Institution: Université de Sherbrooke
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7201921039