group 4: Environmental Impact in Alzheimer’s Disease

Some factors have been identified to increase the risk to develop Alzheimer’s disease (AD). The most important risk factors, age, family heredity, cannot be changed, but emerging evidence suggests there may be other factors that can be influenced. In people with early-onset AD (less than 5% of patients), a genetic mutation is usually the cause. By contrast, late-onset AD (or sporadic AD, more than 95% of patients) arises from a complex series of brain changes that occur over decades. The causes seem to be the result of a combination of genetic susceptibility, environmental and lifestyle factors.

On the basis of our respective experiences, the principal objective of the team is to characterize in vivo and in vitro, the impact of environmental perturbations in the etiology of AD. We focus in particular on chronic stress and oxidative stress, but also on the impact of epilepsy and chronic exposure to low doses of pesticides.

In parallel, we evaluate innovative strategies to counteract deleterious effects of these risk factors, in particular using intranasal administration and photopharmacology.

Presently, we focus on glucocorticoid receptors (involved in stress responses), metabotropic glutamate receptors (mGlu5 - involved in cerebral oscillation) and on free radicals (involved in oxidative stress and neuroinflammation).

For this purpose, we use chronic AD models (transgenic mouse and Zebrafish lines) and an acute model that we particularly contributed to develop and characterize, the Aβ25-35 model.

These projects are currently supported by public contracts and Foundations (Labex LipSTIC; MUSE2020 – Montpellier Université d’Excellence; La région Occitanie AAP2019; FRM AAP2020; SATT-AxLR) and a collaboration with private pharmaceutic company (Inserm MTA with Corcept Therapeutics).

Catherine Desrumaux, group leader

Research Fellow, Inserm Contact: catherine.desrumaux-piazza(at)umontpellier.fr Phone: 04 67 14 36 89

Laurent Givalois, group leader

Research Fellow, CNRS Associate Professor at the Laval University of Québec city Contact: laurent.givalois(at)umontpellier.fr Phone: 04 67 14 38 14

Nathalie Chevallier

Lecturer, Université de Montpellier Contact: nathalie.chevallier(at)umontpellier.fr Phone: 04 67 14 36 89

Léa Oteagui

PhD Student Contact: lea.otaegui(at)etu.umontpellier.fr Phone: 04 67 14 36 89

Magalie Mathias

Engineer, CDD Contact: magalie.mathias(at)umontellier.fr Phone: 04 67 14 36 89

Charleine Zussy

Post-doctoral Fellow Contact: charleine.zussy(at)umontpellier.fr Phone: 04 67 14 38 14

• Canet G, Pineau F, Zussy C, Hernandez C, Hunt H, Chevallier N, Perrier V, Torrent J, Belanoff JK, Meijer OC, Desrumaux C, Givalois L (2020) Glucocorticoid receptors signaling impairment potentiates amyloid-β oligomers-induced pathology in an acute model of Alzheimer’s disease. FASEB J 34, 1150-1168.
• Lafon PA, Wang Y, Arango-Lievano M, Torrent J, Salvador-Prince L, Mansuy M, Mestre-Francès N, Givalois L, Liu J, Mercader JV, Jeanneteau F, Desrumaux C, Perrier V (2020). Fungicide residues exposure and β-amyloid aggregation in a mouse model of Alzheimer’s disease. Environ Health Persp 128, 17011.
• Canet G, Hernandez C, Zussy C, Chevallier N, Desrumaux C, Givalois L (2019) Is AD a stress-related disorder? Focus on the HPA axis and its promising therapeutic targets. Front Aging Neurosci 11, 269.
• Zub E, Canet G, Garbelli R, Blaquiere M, Rossini L, Pastori C, Sheikh M, Reutelingsperger C, Klement W, de Bock F, Audinat E, Givalois L, Solito E, Marchi N (2019) The GR-ANXA1 pathway is a pathological player and a candidate target in epilepsy. FASEB J 33, 13998-14009.
• Desrumaux CM, Mansuy M, Lemaire S, Przybilski J, Le Guern N, Givalois L, Lagrost L (2018) Brain vitamin E deficiency during development is associated with increased glutamate levels and anxiety in adult mice. Front Behav Neurosci 12, 310.
• Mansuy M, Baille S, Canet G, Borie A, Cohen-Solal C, Vignes M, Perrier V, Chevallier N, Le Guern N, Deckert V, Lagrost L, Givalois L, Desrumaux C (2018) Deletion of plasma Phospholipid Transfer Protein (PLTP) increases microglial phagocytosis and reduces cerebral amyloid-β deposition in the J20 mouse model of Alzheimer's Disease. Oncotarget 9, 19688-703.
• Canet G, Chevallier N, Zussy C, Desrumaux C, Givalois L (2018) Central role of glucocorticoid receptors in Alzheimer's disease and depression. Front Neurosci 12, 739.
• Zussy C, Gómez-Santacana X, Rovira X, De Bundel D, Ferrazzo S, Bosch D, Asede D, Malhaire F, Acher F, Giraldo J, Valjent E, Ehrlich I, Ferraguti F, Pin J-P, Llebaria A, Goudet C (2018) Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4. Mol Psychiatry 23, 509-20.