Effects of systemic PSI administration on catecholaminergic cells in the brain, adrenal medulla and carotid body in Wistar rats.
Traditional Parkinson's disease models in rats have several disadvantages. A promising alternative in terms of a more physiological model was proposed by McNaught et al. [McNaught, K.S., Perl, D.P., Brownell, A.L., Olanow, C.W., 2004. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann. Neurol. 56, 149-162.] inhibiting the proteasomal protein degradation in vivo where they observed in Sprague-Dawley rats distinct symptoms of Parkinson's disease, a typical slow progredient loss of dopaminergic neurons in the substantia nigra and a lack of dopaminergic afferences in the striatum. We administered to Wistar rats a synthetic proteasome inhibitor (PSI) analogous to the published method. Locomotor changes were analysed by a footprint test. Brain slices containing the substantia nigra and the striatum were stained immunohistochemically against tyrosine hydroxylase, neuronal nuclei antigen, glial fibrillary acidic protein, alpha-synuclein and microglia. Standard histological stainings (haematoxylin eosin or Nissl) were also performed. The proteasome inhibitor effect on the glomerular layer of the olfactory bulb, the adrenal medulla and the carotid body was examined. We observed no PSI-induced motor deficits and loss of tyrosine hydroxylase immunoreactivity in the substantia nigra or the striatum. However, we detected a distinct increase of tyrosine hydroxylase immunoreactivity in the glomerular layer of the olfactory bulb and in the adrenal medulla. Our results fall in line with reports of other research groups which failed to reproduce the original report, but here for the first time McNaughts model could not be reproduced in Wistar rats. The observed effects on the olfactory bulb and peripheral catecholaminergic organs speak for an impermeability of the blood brain barrier for PSI.
Hawlitschka
Alexander
A
Institute of Anatomy, Faculty of Medicine, University of Rostock, POB 100888, 18055 Rostock, Germany.
Haas
Stefan J P
SJ
Schmitt
Oliver
O
Weiss
Dieter G
DG
Wree
Andreas
A
D000313:Adrenal Medulla / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002344:Carotid Body / Q000166:cytology* / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002492:Central Nervous System Depressants; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase