Scientists analyse the potential of erythropoietin (EPO) as a treatment for neurological and psychiatric diseases

Vicent Teruel (on the left of the image),   of the Department of Human Anatomy a
Vicent Teruel (on the left of the image), of the Department of Human Anatomy and Embryology, and Juan Nácher, of the Department of Cellular Biology, both from the University of Valencia.
Researchers from eleven centres in Spain, the United States and Germany, including the University of Valencia (UV), INCLIVA and Carlos III Health Institute, have analysed the effect on the human brain of erythropoietin (EPO), a hormone secreted mainly by the kidneys, as well as its potential as therapy for the treatment of neurological and psychiatric diseases.

The results of the research, led by the professor of the Department of Cellular Biology of the UV Juan Nácher, also a member of the BIOTECMED Interdisciplinary Research Structure (UV), member of the Research Group in Psychiatry and Neurodegenerative Diseases of INCLIVA and group leader from the Centre for Mental Health Networking Biomedical Research (CIBERSAM), have been published in the journal Molecular Psychiatry.

The research, which reveals the effects of treatment with erythropoietin (EPO) on the structure, connectivity, plasticity and activity of inhibitory neurons, is the result of collaboration with the Max Planck Institute for Multidisciplinary Sciences in Gottingen , in in which Vicent Teruel, researcher at the Department of Human Anatomy and Embryology of the UV, has also participated.

Most studies on EPO have focused on its role in regulating blood cell production, or haematopoiesis. However, for years, following the results of studies in animal models and clinical trials, there is evidence that EPO also has beneficial effects, independent of haematopoiesis, on cognition, in addition to having neuroprotective and neuroregenerative properties.

The cellular and molecular bases of these EPO effects on the central nervous system have begun to be elucidated through the work of the laboratories of the researchers of this work and others, and reveal a very notable impact of the hormone on the structure and functioning of excitatory neurons, the main components of the brain’s circuits.

"In the present work, we have shown that EPO also has a very relevant effect on inhibitory neurons or interneurons, a neuronal subpopulation that very precisely controls the activity and synchronisation of excitatory neurons. These inhibitory neurons are also important because they are altered in different disorders that affect the nervous system", explains Juan Nácher.

In the work, using state-of-the-art cellular and molecular biology tools, the expression of EPO receptors in inhibitory neurons has been identified and the effects of chronic treatment with EPO on different categories of inhibitory neurons in the hippocampus have been described, a key region for the formation of memory and that is altered in different neurological and psychiatric disorders.

"We have shown that this treatment modifies the molecular interactions between inhibitory and excitatory neurons. It also induces reductions in the structural complexity of interneurons and their connectivity, as well as changes in the molecules that regulate the plasticity of these inhibitory neurons. Furthermore, the treatment decreases the metabolism and activity of the interneurons", adds researcher Juan Nácher.

The results propose that the positive effects of EPO treatment on diseases of the nervous system could be due, at least in part, to a restrictive control of the hormone on inhibitory neurons, which would facilitate the plasticity of excitatory neurons, favouring changes in their connectivity and acting on the balance between excitation and inhibition, which is altered in different diseases of the central nervous system.

Article reference : Curto, Y., Carceller, H., Klimczak, P. et al. Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus. Mol Psychiatry (2024). https://doi.org/10.1038/s41380­’024 -02528-2