KDI tripeptide of γ1 laminin protects rat dopaminergic neurons from 6-OHDA induced toxicity

被引:13
作者
Vaananen, Antti J.
Rauhala, Pekka
Tuominen, Raimo K.
Liesi, Paivi
机构
[1] Univ Helsinki, Dept Biol & Environm Sci Physiol, Brain Lab, Bioctr 3, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Biomed Helsinki, Inst Biomed Pharmacol, Helsinki, Finland
[3] Univ Helsinki, Dept Pharm Pharmacol, Helsinki, Finland
[4] Johnnie B Byrd Sr Alzheimers Ctr & Res Inst, Tampa, FL USA
关键词
dopaminergic neurons; KDI; laminin; neuronal protection; Parkinson's disease; 6-OHDA;
D O I
10.1002/jnr.20961
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Our previous studies indicate that the KDI (Lys-Asp-Ile) tripeptide of gamma 1 laminin protects central neurons from mechanical trauma and excitotoxicity. At least part of the neuroprotective effect of the KD1 tripeptide may be mediated by its inhibitory function on ionotropic glutamate receptors. We studied the protective effect of the KDI tripeptide against 6-hydroxy-dopamine (6-OHDA) induced neurotoxicity in a rat experimental model of Parkinson's disease (PD). We found that a single unilateral injection of the KDI tripeptide into the substantia nigra before an injection of 6-OHDA protected the dopaminergic neurons from the neurotoxicity of 6-OHDA. Compared to rats treated with 6-OHDA alone, the KDI + 6-OHDA-treated substantia nigra was relatively intact with large numbers of dopaminergic neurons present at the injection side. In the rats treated with 6-OHDA alone, no dopaminergic neurons were detected, and the substantia nigra-area at the injection side was filled with blood-containing cavities. Quantification of the rescue effect of the KDI tripeptide indicated that, in animals receiving KDI before 6-OHDA, 33% of tyrosine hydroxylase-positive dopaminergic neurons of the substantia nigra were present as compared to the contralateral non-injected side. In animals receiving 6-OHDA alone, only 1.4% of the tyrosine hydroxylase expressing dopaminergic neurons could be verified. If this much protection were achieved in humans, it would be sufficient to diminish or greatly alleviate the clinical symptoms of PD. We propose that the KDI tripeptide or its derivatives might offer a neuroprotective biological alternative for treatment of PD. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:655 / 665
页数:11
相关论文
共 58 条
[21]   LAMININ IS INDUCED IN ASTROCYTES OF ADULT BRAIN BY INJURY [J].
LIESI, P ;
KAAKKOLA, S ;
DAHL, D ;
VAHERI, A .
EMBO JOURNAL, 1984, 3 (03) :683-686
[22]   Induction of type IV collagen and other basement-membrane-associated proteins after spinal cord injury of the adult rat may participate in formation of the glial scar [J].
Liesi, P ;
Kauppila, T .
EXPERIMENTAL NEUROLOGY, 2002, 173 (01) :31-45
[23]   DO NEURONS IN THE VERTEBRATE CNS MIGRATE ON LAMININ [J].
LIESI, P .
EMBO JOURNAL, 1985, 4 (05) :1163-1170
[24]   Neurons and glial cells of the embryonic human brain and spinal cord express multiple and distinct isoforms of laminin [J].
Liesi, P ;
Fried, G ;
Stewart, RR .
JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 64 (02) :144-167
[25]   Biologically active sequence (KDI) mediates the neurite outgrowth function of the gamma-1 chain of laminin-1 [J].
Liesi, P ;
Laatikainen, T ;
Wright, JM .
JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 66 (06) :1047-1053
[26]   IDENTIFICATION OF A NEURITE OUTGROWTH-PROMOTING DOMAIN OF LAMININ USING SYNTHETIC PEPTIDES [J].
LIESI, P ;
NARVANEN, A ;
SOOS, J ;
SARIOLA, H ;
SNOUNOU, G .
FEBS LETTERS, 1989, 244 (01) :141-148
[28]   IS ASTROCYTE LAMININ INVOLVED IN AXON GUIDANCE IN THE MAMMALIAN CNS [J].
LIESI, P ;
SILVER, J .
DEVELOPMENTAL BIOLOGY, 1988, 130 (02) :774-785
[29]   DOMAIN-SPECIFIC ANTIBODIES AGAINST THE B2 CHAIN OF LAMININ INHIBIT NEURONAL MIGRATION IN THE NEONATAL RAT CEREBELLUM [J].
LIESI, P ;
HAGER, G ;
DODT, HU ;
SEPPALA, I ;
ZIEGLGANSBERGER, W .
JOURNAL OF NEUROSCIENCE RESEARCH, 1995, 40 (02) :199-206
[30]  
Lindvall Olle, 2004, NeuroRx, V1, P382