SubsidieMeestersResolving sEx DIffeREnces in proCessing sensory informaTion
REDIRECT aims to investigate how prenatal cannabis exposure affects sensory information processing deficits in males and females, to develop sex-specific therapies for mental disorders.
Projectdetails
Introduction
Mental disorders are associated with abnormal sensory information processing (SIP) at preadolescence, especially in males. Aberrant SIP is a neutral cross-disorder trait that can be translated between humans and animals and assessed as the inability to prevent/gate an overload of irrelevant information.
Research Gaps
The mechanisms underlying physiological and pathological SIP variability are unexplored. Particularly, the causative role of hyperdopaminergia, key to SIP deficits, has never been tested by isolating, spatially and temporally, this single neural component.
Key Questions
- How does this trait evolve into a mental disorder?
- Why does it occur more often in males?
Project Overview
REDIRECT will capitalize on our rodent model of prenatal cannabis exposure (PCE), which is the first of its kind to offer, at preadolescence, a sex bias in susceptibility to SIP deficits upon acute exposure to stress or cannabis. This animal model is amenable to molecular interrogation to probe causality for those resilience-promoting factors preventing females from developing hyperdopaminergia and SIP deficits.
Methodology
By combining viral strategies to trace and probe cell-type specific input-output reorganization of dopamine circuits (Aim 1), with single-cell transcriptome analyses (Aim 2), REDIRECT will decipher how female sex imposes distinct molecular changes to neurons and circuits, which are key to preventing the etiopathogenesis of SIP disorders.
Candidate Genes
By testing selected candidate genes to probe causality for how sex modulates genes, developmental trajectories, and behaviour, we will decode (Aim 3) how discrete dopaminergic circuits can be reprogrammed sex-dependently.
Expected Outcomes
REDIRECT will causally disentangle how sex differently affects genes, circuits, and behaviour to inform novel sex-specific and age-tailored therapies for SIP deficits, a cross-disorder trait typical of common and severe mental illnesses, including autism, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and schizophrenia.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.999.138 |
| Totale projectbegroting | € 1.999.138 |
Tijdlijn
| Startdatum | 1-6-2023 |
| Einddatum | 31-5-2028 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- UNIVERSITA DEGLI STUDI DI CAGLIARIpenvoerder
Land(en)
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