Striatopallidal neurons are selectively protected by neurturin in an excitotoxic model of Huntington's disease.
Excitotoxicity has been involved in the pathogenesis of several neurodegenerative disorders. Using intrastriatal quinolinic acid (QUIN) injection as an animal model of Huntington's disease, we attempt to identify the neurotransmitter phenotype of striatal projection neurons protected by neurturin (NRTN). Control or NRTN-secreting cell lines were grafted in the striatum before QUIN injection and striatal projection neurons were examined by retrograde Fluorogold labeling and in situ hybridization. Intrastriatal grafting of NRTN-secreting cell line selectively prevented the loss of striatopallidal neurons and also the decrease in the mRNA levels for their markers (glutamic acid decarboxylase 67 and preproenkephalin) induced by QUIN, without affecting striatonigral neurons. Thus, our findings show that NRTN is a selective neuroprotective factor for striatopallidal neurons, suggesting that it might be a candidate for the treatment of movement disorders in which this neuronal population is affected.
Marco
Sònia
S
Departament de Biologia Celcenter dotlular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Casanova 143, E-08036 Barcelona, Spain.
Pérez-Navarro
Esther
E
Tolosa
Eduard
E
Arenas
Ernest
E
Alberch
Jordi
J
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics; D005917:Globus Pallidus / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D005968:Glutamate Decarboxylase / Q000235:genetics; D006816:Huntington Disease / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D051101:Neurturin; D011498:Protein Precursors / Q000235:genetics; D017378:Quinolinic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015320:Tachykinins / Q000235:genetics
D004745:Enkephalins; D007527:Isoenzymes; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D051101:Neurturin; C495057:Nrtn protein, rat; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; C033660:preproenkephalin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D017378:Quinolinic Acid