Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration
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Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration. / Miskowiak, Kamilla; Inkster, Becky; O'Sullivan, Ursula; Selvaraj, Sudhakar; Goodwin, Guy M; Harmer, Catherine J.
I: Experimental Brain Research, Bind 184, Nr. 3, 01.2008, s. 313-21.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration
AU - Miskowiak, Kamilla
AU - Inkster, Becky
AU - O'Sullivan, Ursula
AU - Selvaraj, Sudhakar
AU - Goodwin, Guy M
AU - Harmer, Catherine J
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Adult
KW - Brain Mapping
KW - Cerebral Cortex
KW - Cerebrovascular Circulation
KW - Cognition
KW - Cohort Studies
KW - Erythropoietin
KW - Female
KW - Frontal Lobe
KW - Gyrus Cinguli
KW - Humans
KW - Magnetic Resonance Imaging
KW - Male
KW - Memory, Short-Term
KW - Nerve Growth Factors
KW - Nerve Net
KW - Neuropsychological Tests
KW - Nootropic Agents
KW - Parietal Lobe
KW - Thinking
KW - Time
KW - Time Factors
KW - Treatment Outcome
KW - Verbal Behavior
KW - Clinical Trial
KW - Comparative Study
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00221-007-1102-1
DO - 10.1007/s00221-007-1102-1
M3 - Journal article
C2 - 17828390
VL - 184
SP - 313
EP - 321
JO - Experimental Brain Research
JF - Experimental Brain Research
SN - 0014-4819
IS - 3
ER -
ID: 184777678