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Infusion of CRHR1 agonists in the lateral septum to rescue social preference in a mouse model of schizophrenia

Project description

Novel strategy for treating social anxiety disorders

Schizophrenia and social anxiety disorders impair social interaction, often leading to isolation, loss of employment, or inability to form relationships. Despite the increasing number of cases, no specific medications exist to treat extreme introversion. The ERC-funded SocialPref project builds on the previous discovery of a neuronal circuit between the prefrontal cortex and lateral septum that helps regulate social behaviour. In schizophrenia models, this pathway involves the corticotropin-releasing hormone receptor (CRHR1) and is disrupted, leading to abnormal social novelty preference. The project will test whether CRHR1 agonists can restore social behaviour in a schizophrenia mouse model. Findings may accelerate development of innovative therapies for debilitating mental health conditions.

Objective

"Patients affected with schizophrenia or social anxiety disorders such as separation anxiety or avoidant personality disorders often exhibit difficulties to socially interact, particularly with novel individuals. Altered social interactions impair their day-to-day life and often prevent them from having families or holding on to their jobs. In addition, the number of individuals living as recluses and suffering from the Hikkimori syndrome has sharply increased since the COVID pandemic. Currently, there is no dedicated medication to treat the crippling introversion associated with these disorders.

We discovered a neuronal circuit regulating social preferences through the activation of the corticotropin-related hormone receptor 1 in the lateral septum (LS). Specifically, we demonstrated through a combination of electrophysiological, chemogenetic, optogenetic, calcium recording and gene silencing techniques that the release of CRH from prefrontal cortex (PFC) neurons into LS suppresses social interaction with familiar mice. This circuit therefore contributes to the social novelty preference exhibited by adult mice. based on these results, we presented a patent titled ""CRHR1 agonists for use in the treatment of social anxiety disorders"". In addition, preliminary data shows that social novelty preference as well as CRH signaling from the PFC to LS is dysregulated in the Df16(A)+/- mouse model of schizophrenia.

In order to further interest for our patent from pharmaceutical companies, we would like to conduct a pre-clinical study testing whether infusion of CRHR1 agonists in the septum of Df16(A)+/- mice can rescue social novelty preference and improve social interactions in this model. Our overarching goal is to facilitate the development of new treatments for mental health disorder patients suffering from extreme introversion."

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2024-POC

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Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
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.

€ 150 000,00
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost

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