Summary
Neuropsychiatric and neurodevelopmental disorders are a heterogeneous group of mental diseases affecting about 1 billion people worldwide. Common alterations are in the cognitive and social domains, having a critical impact on the public health, daily life, and long-term outcomes of affected patients. Unfortunately, efficient pharmacological interventions are still missing. The serotonin transporter (SERT) re-uptakes serotonin after synaptic release and is an important clinical target. SERT is widely expressed in the prefrontal cortex (PFC), an area profoundly engaged in socio-cognitive functions, and can be targeted by inhibitors -drugs acting by blocking the transporter- or by releasers- drugs acting as a substrate of SERT and then reversing its transport direction. The SERT releaser MDMA showed promising results for treating social dysfunctions in post-traumatic stress disorder and autism spectrum disorders and its pro-social effect seems dependent on SERT-reverse transport. Considering the efficacy of the SERT-releaser MDMA in modulating social dysfunctions, together with the need of SERT-reverse functions in mediating MDMA pro-social effects, and the role of the PFC in the regulation of socio-cognitive functions, the aim of PRESERT is to evaluate the impact of SERT on social cognition in mice. To achieve this overarching goal, PRESERT is divided into three specific objectives: i) investigating the impact of the PFC-expressed SERT on social cognition, ii) identifying the origin and connectivity of the underlying SERT-expressing circuits, and iii) evaluating if social cognition can be differentially modulated by the reverse transport (i.e. “efflux”) or the simple inhibition of SERT. As a direct consequence, PRESERT has the potential to link SERT, its molecular functions, and the underlying brain circuits to specific aspects of social cognition setting the ground for the development of innovative treatments for neuropsychiatric disorders.
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| Web resources: | https://cordis.europa.eu/project/id/101147370 |
| Start date: | 01-04-2025 |
| End date: | 31-03-2027 |
| Total budget - Public funding: | - 172 750,00 Euro |
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Original description
Neuropsychiatric and neurodevelopmental disorders are a heterogeneous group of mental diseases affecting about 1 billion people worldwide. Common alterations are in the cognitive and social domains, having a critical impact on the public health, daily life, and long-term outcomes of affected patients. Unfortunately, efficient pharmacological interventions are still missing. The serotonin transporter (SERT) re-uptakes serotonin after synaptic release and is an important clinical target. SERT is widely expressed in the prefrontal cortex (PFC), an area profoundly engaged in socio-cognitive functions, and can be targeted by inhibitors -drugs acting by blocking the transporter- or by releasers- drugs acting as a substrate of SERT and then reversing its transport direction. The SERT releaser MDMA showed promising results for treating social dysfunctions in post-traumatic stress disorder and autism spectrum disorders and its pro-social effect seems dependent on SERT-reverse transport. Considering the efficacy of the SERT-releaser MDMA in modulating social dysfunctions, together with the need of SERT-reverse functions in mediating MDMA pro-social effects, and the role of the PFC in the regulation of socio-cognitive functions, the aim of PRESERT is to evaluate the impact of SERT on social cognition in mice. To achieve this overarching goal, PRESERT is divided into three specific objectives: i) investigating the impact of the PFC-expressed SERT on social cognition, ii) identifying the origin and connectivity of the underlying SERT-expressing circuits, and iii) evaluating if social cognition can be differentially modulated by the reverse transport (i.e. “efflux”) or the simple inhibition of SERT. As a direct consequence, PRESERT has the potential to link SERT, its molecular functions, and the underlying brain circuits to specific aspects of social cognition setting the ground for the development of innovative treatments for neuropsychiatric disorders.Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
02-10-2024
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