Descripción del proyecto
Estudio de los mecanismos de la mejora del rendimiento cognitivo en condiciones de hipoxia
La alteración de la neuroplasticidad está relacionada con el deterioro cognitivo. Sin embargo, se desconocen los mecanismos que subyacen a la neuroplasticidad, lo que obstaculiza el descubrimiento de nuevos tratamientos. En el proyecto ALTIBRAIN, financiado con fondos europeos, se estudiará un nuevo modelo que vincula la concentración de oxígeno, el aumento de la eritropoyetina (EPO) en el cerebro, la neuroplasticidad y la cognición. Su equipo se basará en el descubrimiento previo de que la regulación al alza de la EPO en el cerebro, en condiciones de hipoxia, aumenta la neuroplasticidad y la cognición en ratones. En ALTIBRAIN se determinará si la regulación al alza de la EPO en el cerebro debida a la hipoxia es el mecanismo responsable de la neuroplasticidad a largo plazo y el aumento de las funciones cognitivas en seres humanos. Sus investigadores emplearán un enfoque de investigación aplicable multidisciplinario en seres humanos y ratones, a fin de estudiar los efectos de la hipoxia combinada con el entrenamiento cognitivo en la expresión de la EPO cerebral y el rendimiento cognitivo.
Objetivo
Cognitive decline is an urgent strategic treatment target to improve the lives of people with neuropsychiatric disorders and reduce associated societal costs but treatments with robust and long-lasting efficacy are essentially lacking. Neuroplasticity is pivotal for cognitive functions and its disruption is involved in cognitive decline. However, the mechanisms underlying long-lasting neuroplasticity are unknown, which impedes the discovery of effective treatments. To address this challenge, I have conducted multidisciplinary research over the past 15 years into the cognitive and neurobiological effects of erythropoietin (EPO), a body-own protein involved in neurodevelopment, neuroprotection and cognition. We discovered that upregulation of EPO in the brain by low ambient oxygen increased neuroplasticity and cognition in mice. Building on this discovery, ALTIBRAIN will test a novel model linking oxygen manipulation, increased brain EPO, neuroplasticity and cognition. Specifically, ALTIBRAIN will determine whether upregulation of brain EPO by low ambient oxygen is a novel mechanism of long-lasting neuroplasticity and increased cognitive functions. We will achieve this ambitious goal using a multidisciplinary translational research approach combining cutting-edge methods from neuropsychology, neuroimaging and neuroscience. In parallel studies in humans and mice, we will investigate whether 3-week intermittent low ambient oxygen combined with cognitive training induces expression of brain EPO sufficient to produce similar effects to those, which I found upon exogenous EPO treatment. We expect long-lasting increase in cognitive performance, hippocampal volume and function and in differentiation/maturation of neural progenitor cells and dendritic spines. The findings can lead to a breakthrough in the understanding of mechanisms underlying enduring neuroplasticity and a paradigm shift in treatment strategies targeting cognitive decline.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
1165 Kobenhavn
Dinamarca