Erythropoietin: a candidate compound for neuroprotection in schizophrenia.
Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.
Ehrenreich
H
H
Max-Planck-Institute for Experimental Medicine and Department of Psychiatry, Georg-August-University, Goettingen, Germany. ehrenreich@em.mpg.de
Degner
D
D
Meller
J
J
Brines
M
M
Béhé
M
M
Hasselblatt
M
M
Woldt
H
H
Falkai
P
P
Knerlich
F
F
Jacob
S
S
von Ahsen
N
N
Maier
W
W
Brück
W
W
Rüther
E
E
Cerami
A
A
Becker
W
W
Sirén
A-L
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects; D004921:Erythropoietin / Q000493:pharmacokinetics*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007205:Indium Radioisotopes; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000493:pharmacokinetics*; D051381:Rats; D011994:Recombinant Proteins; D012563:Schizophrenia, Paranoid / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D007205:Indium Radioisotopes; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D006220:Haloperidol