Project description
Studying mechanisms of cognitive performance improvement under hypoxia conditions
Disruption in neuroplasticity is linked to cognitive decline, but the mechanisms underlying neuroplasticity are unknown, preventing the discovery of novel treatments. The EU-funded ALTIBRAIN project will study a novel model that links oxygen level, increased brain erythropoietin (EPO), neuroplasticity and cognition. The project will build on the previous discovery that EPO upregulation in the brain, using low ambient oxygen, increases neuroplasticity and cognition in mice. ALTIBRAIN will determine whether brain EPO upregulation by low oxygen is the mechanism of long-lasting neuroplasticity and increased cognitive functions in humans. Using a multidisciplinary translational research approach in humans and mice, the researchers will investigate the effects of low ambient oxygen combined with cognitive training on the expression of brain EPO and cognitive performance.
Objective
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.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
1165 Kobenhavn
Denmark