Altitude-like hypoxia cognition training to target brain erythropoietin as a novel mechanism of long-lasting enhancement of neuroplasticity and cognitive functions

Introduction

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.

Research Background

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.

Key Discoveries

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.

Project Objectives

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:

1. Neuropsychology
2. Neuroimaging
3. Neuroscience

Experimental Approach

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.

Expected Outcomes

We expect a 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.