Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration
Abstract
Erythropoietin (Epo) has neuroprotective and neurotrophic effects and improves cognitive function in animal models of neurodegenerative and neuropsychiatric illness. In humans, weekly Epo administration over 3 months improves cognitive function in schizophrenia. The neural underpinnings and time-course of this effect of Epo are currently unknown. It is also unclear whether the cognitive improvement reflects direct neurobiological actions or is secondary to hematological effects. We therefore assessed the actions of single administration of Epo (40,000 IU) vs. saline to healthy volunteers on cognitive and neural measures of executive function using a verbal fluency task and N-back working memory (WM) paradigm during functional magnetic resonance imaging (fMRI) on day 3 and 7 after administration in two separate cohorts of subjects. Epo modulated neuronal response in a fronto-parietal network during WM performance at both time points; on day 3 after administration, activation was increased in left-hemisphere frontal and cingulate cortex and reduced in the right parietal cortex; in contrast, neural response was enhanced in a right-lateralized fronto-parietal network and reduced in left-side regions 1 week post-administration. In addition, Epo-treated volunteers displayed improved verbal fluency performance 1 week post-administration. These effects occurred in the absence of changes in hematological measures suggesting that they reflect direct neurobiological actions of Epo. The findings are consistent with enduring effects of Epo on neurotrophic signaling and induction of neurochemical changes over time in neural networks typically affected in neuropsychiatric illness. The present study supports the notion that Epo may have clinical applications in the treatment of psychiatric disorder characterized by cognitive dysfunction.
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In healthy volunteers, erythropoietin modulated neuronal activity in a frontoparietal network during working memory and improved executive function (verbal fluency) 1 week after a single high-dose administration of 40,000 IU.
“In healthy volunteers, EPO modulated neuronal activity in a frontoparietal network during working memory and improved executive function (i.e. verbal fluency) 1 week after a single high-dose administration (40,000 IU) [96].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [96]
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- Authors
- Miskowiak, K., Inkster, B., O’Sullivan, U., Selvaraj, S., Goodwin, G. M., & Harmer, C. J.
- Affiliations
- University of Oxford (GB)
- Warneford Hospital (GB)
- Corresponding author
- Miskowiak, Kamilla
- Venue
- Experimental Brain Research
- Published
- 2007-09-08
- Volume
- 184
- Issue
- 3
- Pages
- 313-321
- ISSN
- 0014-4819 (ISSN-L)
- 1432-1106
- OpenAlex
- W2018591234
- Cited by
- 59
- References
- 37
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Experimental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- erythropoietin, executive function, working memory, verbal fluency, frontoparietal network, hemispheric lateralization, cingulate cortex, parietal cortex, neurotrophic signaling, cognitive impairment, neuropsychiatric disorders, healthy volunteers
- MeSH terms
- Adult, Brain Mapping, Cerebral Cortex, Cerebrovascular Circulation, Cognition, Erythropoietin, Female, Frontal Lobe, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Nerve Growth Factors, Nerve Net, Neuropsychological Tests, Parietal Lobe, Thinking, Time, Time Factors, Verbal Behavior, Cohort Studies, Treatment Outcome, Nootropic Agents
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