Time-dependent alterations of peripheral immune parameters after nigrostriatal dopamine depletion in a rat model of Parkinson's disease.
Dysfunction of the central dopaminergic system is associated with neurodegenerative disorders and mental illnesses such as Parkinson's disease and schizophrenia. Patients suffering from these diseases were reported to exhibit altered immune functions compared to healthy subjects and imbalance of the central dopaminergic system has been suggested as one causative factor for the immune disturbances. However, it is unclear whether the observed immune changes are primary or secondary to the disease. Here we demonstrate that central dopamine (DA) depletion in a rat model of Parkinson's disease induced transient changes in blood leukocyte distribution and cytokine production that were apparent until four weeks after bilateral intrastriatal administration of the neurotoxin 6-hydroxydopamine (6-OHDA). Eight weeks after treatment, no differences in blood immune parameters were anymore evident between neurotoxin-treated and control animals. Nevertheless, animals with a widespread damage of dopaminergic neurons in the nigrostriatal system showed an exacerbated pro-inflammatory response following in vivo challenge with bacterial lipopolysaccharide. Our data indicate that peripheral immune perturbations in the early phase after intrastriatal 6-OHDA administration might have been related to the neurodegenerative process itself whereas the increased sensitivity to the inflammatory stimulus seems to have resulted from an impaired dopaminergic control of prolactin (PRL) and corticosterone (CORT) secretion. The findings demonstrate that the brain dopaminergic system is involved in peripheral immune regulation and suggest that central dopaminergic hypoactivity bears the risk of excessive inflammation, e.g., during infection or tissue injury.
Engler
Harald
H
Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. harald.engler@uk-essen.de
Doenlen
Raphael
R
Riether
Carsten
C
Engler
Andrea
A
Niemi
Maj-Britt
MB
Besedovsky
Hugo O
HO
del Rey
Adriana
A
Pacheco-López
Gustavo
G
Feldon
Joram
J
Schedlowski
Manfred
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D016207:Cytokines; D008070:Lipopolysaccharides; D016627:Oxidopamine; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase; D003891:Desipramine; D004298:Dopamine; D003345:Corticosterone