Erythropoietin Enhances Hippocampal Response During Memory Retrieval in Humans

Overview

Journal J Neurosci

Specialty Neurology

Date 2007 Mar 16

PMID 17360900

Citations 54

Authors

Kamilla Miskowiak

Ursula OSullivan

Catherine J Harmer

Affiliations

Soon will be listed here.

Abstract

Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment of neurological and psychiatric disorders. The current study therefore aimed to explore the effects of Epo on neural and behavioral measures of hippocampal function in humans using a functional magnetic resonance imaging paradigm. Volunteers were randomized to receive intravenous injection of Epo (40,000 IU) or saline in a between-subjects, double-blind, randomized design. Neural response during picture encoding and retrieval was tested 1 week later. Epo increased hippocampus response during picture retrieval (n = 11) compared with placebo (n = 12; p = 0.04) independent of changes in hematocrit. This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders.

Citing Articles

Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats.

Caliskan H, Onal D, Nalcaci E BMC Immunol. 2024; 25(1):75.

PMID: 39523336 PMC: 11552158. DOI: 10.1186/s12865-024-00665-5.

Effects of cognitive training under hypoxia on cognitive proficiency and neuroplasticity in remitted patients with mood disorders and healthy individuals: ALTIBRAIN study protocol for a randomized controlled trial.

Miskowiak K, Damgaard V, Schandorff J, Macoveanu J, Knudsen G, Johansen A Trials. 2024; 25(1):648.

PMID: 39363230 PMC: 11447976. DOI: 10.1186/s13063-024-08463-5.

Role of erythropoietin in the treatment of Alzheimer's disease: the story so far.

Kalluru P, Bhavanthi S, Vashist S, Gopavaram R, Mamilla M, Sharma S Ann Med Surg (Lond). 2024; 86(6):3608-3614.

PMID: 38846819 PMC: 11152865. DOI: 10.1097/MS9.0000000000002113.

Synergism of Carbamoylated Erythropoietin and Insulin-like Growth Factor-1 in Immediate Early Gene Expression.

Rothschadl M, Sathyanesan M, Newton S Life (Basel). 2023; 13(9).

PMID: 37763230 PMC: 10532867. DOI: 10.3390/life13091826.

Erythropoietin re-wires cognition-associated transcriptional networks.

Singh M, Zhao Y, Daguano Gastaldi V, Wojcik S, Curto Y, Kawaguchi R Nat Commun. 2023; 14(1):4777.

PMID: 37604818 PMC: 10442354. DOI: 10.1038/s41467-023-40332-8.

References

Lupien S, De Leon M, De Santi S, Convit A, Tarshish C, Nair N . Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci. 1999; 1(1):69-73. DOI: 10.1038/271. View

Lancaster J, Woldorff M, Parsons L, Liotti M, Freitas C, Rainey L . Automated Talairach atlas labels for functional brain mapping. Hum Brain Mapp. 2000; 10(3):120-31. PMC: 6871915. DOI: 10.1002/1097-0193(200007)10:3<120::aid-hbm30>3.0.co;2-8. View

Brines M, Ghezzi P, Keenan S, Agnello D, De Lanerolle N, Cerami C . Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A. 2000; 97(19):10526-31. PMC: 27058. DOI: 10.1073/pnas.97.19.10526. View

Jenkinson M, Smith S . A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001; 5(2):143-56. DOI: 10.1016/s1361-8415(01)00036-6. View

Birn R, Cox R, Bandettini P . Detection versus estimation in event-related fMRI: choosing the optimal stimulus timing. Neuroimage. 2002; 15(1):252-64. DOI: 10.1006/nimg.2001.0964. View

Cansino S, Maquet P, Dolan R, Rugg M . Brain activity underlying encoding and retrieval of source memory. Cereb Cortex. 2002; 12(10):1048-56. DOI: 10.1093/cercor/12.10.1048. View

Jenkinson M, Bannister P, Brady M, Smith S . Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage. 2002; 17(2):825-41. DOI: 10.1016/s1053-8119(02)91132-8. View

Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M . Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002; 8(8):495-505. PMC: 2040012. View

Malberg J, Duman R . Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003; 28(9):1562-71. DOI: 10.1038/sj.npp.1300234. View

10.

Maldjian J, Laurienti P, Kraft R, Burdette J . An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage. 2003; 19(3):1233-9. DOI: 10.1016/s1053-8119(03)00169-1. View

11.

Hariri A, Goldberg T, Mattay V, Kolachana B, Callicott J, Egan M . Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci. 2003; 23(17):6690-4. PMC: 6740735. View

12.

Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S . Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003; 301(5634):805-9. DOI: 10.1126/science.1083328. View

13.

JACOBSON L, GOLDWASSER E, Fried W, PLZAK L . Studies on erythropoiesis. VII. The role of the kidney in the production of erythropoietin. Trans Assoc Am Physicians. 1957; 70:305-17. View

14.

Ehrenreich H, Degner D, Meller J, Brines M, Behe M, Hasselblatt M . Erythropoietin: a candidate compound for neuroprotection in schizophrenia. Mol Psychiatry. 2003; 9(1):42-54. DOI: 10.1038/sj.mp.4001442. View

15.

Chambers R, Potenza M, Hoffman R, Miranker W . Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks. Neuropsychopharmacology. 2004; 29(4):747-58. DOI: 10.1038/sj.npp.1300358. View

16.

Mogensen J, Miskowiak K, Sorensen T, Lind C, Olsen N, Springborg J . Erythropoietin improves place learning in fimbria-fornix-transected rats and modifies the search pattern of normal rats. Pharmacol Biochem Behav. 2004; 77(2):381-90. DOI: 10.1016/j.pbb.2003.11.017. View

17.

Kitraki E, Kremmyda O, Youlatos D, Alexis M, Kittas C . Spatial performance and corticosteroid receptor status in the 21-day restraint stress paradigm. Ann N Y Acad Sci. 2004; 1018:323-7. DOI: 10.1196/annals.1296.039. View

18.

Campbell S, MacQueen G . The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2005; 29(6):417-26. PMC: 524959. View

19.

Viviani B, Bartesaghi S, Corsini E, Villa P, Ghezzi P, Garau A . Erythropoietin protects primary hippocampal neurons increasing the expression of brain-derived neurotrophic factor. J Neurochem. 2005; 93(2):412-21. DOI: 10.1111/j.1471-4159.2005.03033.x. View

20.

Brines M, Cerami A . Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci. 2005; 6(6):484-94. DOI: 10.1038/nrn1687. View