Neuroprotection of striatal neurons against kainate excitotoxicity by neurotrophins and GDNF family members.
Neurotrophic factors are regarded as potential therapeutic tools in neurodegenerative disorders. Here, we analysed the protective effects of brain-derived neurotrophic factor, neurotrophin-3, glial cell line-derived neurotrophic factor and neurturin against the excitotoxic damage induced by kainate in striatal neurons in vitro and in vivo. Our results show that the decrease in the number of cultured striatal calbindin-positive neurons induced by kainate was prevented by treatment with any of these factors. To characterize their protective effects in vivo, cell lines overexpressing brain-derived neurotrophic factor, neurotrophin-3, glial cell line-derived neurotrophic factor or neurturin were grafted into the striatum. We found that the numbers of striatal projection neurons (calbindin-positive) and striatal interneurons (parvalbumin- or choline acetyltransferase-positive) were differentially decreased after kainate lesion. These neurotrophic factors prevented the loss of striatal projection neurons and interneurons with differing efficiency: brain-derived neurotrophic factor was the most efficient, whereas neurturin was the least. Our findings show that brain-derived neurotrophic factor, neurotrophin-3, glial cell line-derived neurotrophic factor and neurturin have specific neuroprotective profiles in striatal neurons and indicate that they are specific modulators of the survival of distinct subsets of striatal neurons in pathophysiological conditions.
Gratacòs
E
E
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Barcelona, Spain.
Pérez-Navarro
E
E
Tolosa
E
E
Arenas
E
E
Alberch
J
J
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D064026:Calbindins; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D029721:Drosophila Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D007395:Interneurons / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D005810:Multigene Family; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D029721:Drosophila Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011518:Proto-Oncogene Proteins; D064030:S100 Calcium Binding Protein G; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D007608:Kainic Acid