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Hyper-emotionality after neurodegenerative loss of inhibition of the amygdala

Objective

"I propose to test how hyper-anxiety in Alzheimer's disease (AD) patients is caused by neurodegeneration in the amygdala, our ""center of fear"", by comparing with a unique group of Urbach Wiethe disease (UWD) patients with bilateral neurodegeneration of the amygdala (BLA) for which I also construct an animal model. UWD is caused by a very rare genetic mutation occurring in only a handful of individuals worldwide. My host in Lausanne has gained access, however, to a uniquely large group of UWD patients in South-Africa (>40) where the mutation has spread for 400 years in Dutch settlers. Our collaborators at Cape Town University have found, in anatomical & functional MRI and special behavioral tests, how specific loss of inhibitory projections from the basolateral (BLA) onto the central part of the amygdala (CeA) causes hyper-anxiety in UWD. Based upon recently reported BLA neurodegeneration in AD patients, I hypothesize a crucial BLA role in hyper-anxiety of AD patients. I plan to test this in AD patients with clinical collaborators in Lausanne and, to test this hypothesis causally, I have started to opto,- anc chemogenetically decrease BLA function in an animal model.
In addition, in Lausanne a stronger hyper-anxiety was observed in AD patients with insecurely attached personality profiles. As my host lab has established an inhibitory role of oxytocin (OT) in the CeA, I hypothesize a decreased OT signaling in CeA of these patients, adding to the anxiety already caused by the BLA loss. I plan to test this both in AD and UWD patients by correlating attachment profiles with OT levels (in blood & cerebrospinal fluid) and anxiety levels & BLA damage (MRI). I will use opto&chemogenetic targeting of OT signaling in animals for a causal relation. This multidisciplinary and translational approach can give a deeper understanding of the role of the amygdala in hyper-anxiety in human patients, and provide a firm neurobiological basis for applying OT to treat anxiety disorders.
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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2015

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Coordinator

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 42 069,30
Address
VIA MOREGO 30
16163 GENOVA
Italy

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Region
Nord-Ovest Liguria Genova
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 42 069,30

Participants (1)

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