Effect of 6-hydroxydopamine treatment on kynurenine aminotransferase-I (KAT-I) immunoreactivity of neurons and glial cells in the rat substantia nigra.
Parkinson's disease (PD), a progressive neurodegenerative disorder, is characterized by a preferential loss of dopaminergic neurons in the substantia nigra pars compacta (SNPC). Neurons in the SNPC are known to express tyrosine hydroxylase (TH); therefore, in a commonly used PD model, 6-hydroxydopamine (6-OHDA), a selective catecholamine neurotoxin, induces neuronal death in SNPC. We have shown with immunohistochemical techniques that kynurenine aminotransferase-I (KAT-I), the enzyme taking part in the formation of kynurenic acid (KYNA)--the only known endogenous selective NMDA receptor antagonist and a potent neuroprotective agent--is also expressed in the rat SNPC. We found that KAT-I and TH co-exist in the very same neurons of SNPC and that 6-OHDA injected into the lateral ventricle produced loss of the majority of nigral neurons. Densitometric analysis proved that, in consequence of 6-OHDA treatment, not only TH but also KAT-I immunoreactivity diminished considerably in the remaining SNPC neurons. Astrocytes in the substantia nigra were found to express KAT-I under normal conditions; the amount of this enzyme increased after administration of 6-OHDA, whereas microglial cells became KAT-I immunoreactive only after 6-OHDA treatment. Since intrinsic KYNA in SNPC neurons is perceptibly insufficient to protect them from the deleterious effect of 6-OHDA, it is hypothesized that biochemical approaches which increase KYNA content of the central nervous system might prevent the deleterious effect of 6-OHDA and, supposedly, also the neuronal degradation characterizing PD.
Knyihár-Csillik
Elizabeth
E
Department of Neurology, Albert Szent-Györgyi Medical and Pharmaceutical Center, University of Szeged, 6701, Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu
Chadaide
Zoltan
Z
Mihály
András
A
Krisztin-Péva
Beata
B
Fenyo
Robert
R
Vécsei
László
L
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000201:enzymology* / Q000473:pathology; D000637:Transaminases / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D018663:Adrenergic Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase