Lippincott Williams & Wilkins, Inc., Philadelphia
Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5 Prevent the Death of Striatal Projection Neurons in a Rodent Model of Huntington's Disease
Article first published online: 4 JAN 2002
Journal of Neurochemistry
Volume 75, Issue 5, pages 2190–2199, November 2000
How to Cite
Pérez-Navarro, E., Canudas, A. M., Åkerud, P., Alberch, J. and Arenas, E. (2000), Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5 Prevent the Death of Striatal Projection Neurons in a Rodent Model of Huntington's Disease. Journal of Neurochemistry, 75: 2190–2199. doi: 10.1046/j.1471-4159.2000.0752190.x
Abbreviations used: BDNF, brain-derived neurotrophic factor; DYN, prodynorphin; F3A-MT, F3A-NT3, F3A-NT4/5, and F3N-BDNF, mock-transfected, neurotrophin-3-transfected, neurotrophin-4/5-transfected, and brain-derived neurotrophic factor-transfected, respectively, Fischer-344 rat 3T3 fibroblasts; GAD, glutamic acid decarboxylase 67; HD, Huntington's disease; NT-3, neurotrophin-3; NT-4/5, neurotrophin-4/5; PPE, preproenkephalin; PPTA, preprotachykinin; QUIN, quinolinate; TdT, terminal deoxynucleotidyl transferase; TUNEL, terminal deoxynucleotidyl transferase-mediated UTP nick end-labeling.
- Issue published online: 4 JAN 2002
- Article first published online: 4 JAN 2002
- Rat striatum;
Abstract: Intrastriatal injection of quinolinate has been proven to be a very useful animal model to study the pathogenesis and treatment of Huntington's disease. To determine whether growth factors of the neurotrophin family are able to prevent the degeneration of striatal projection neurons, cell lines expressing brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) were grafted in the adult rat striatum before quinolinate injection. Three days after lesioning, ongoing cell death was assessed by in situ detection of DNA fragmentation. In animals grafted with the control cell line, quinolinate injection induced a gradual cell loss that was differentially prevented by intrastriatal grafting of BDNF-, NT-3-, or NT-4/5-secreting cells. Seven days after lesioning, we characterized striatal projection neurons that were protected by neurotrophins. Quinolinate injection, alone or in combination with the control cell line, induced a selective loss of striatal projection neurons. Grafting of a BDNF-secreting cell line prevented the loss of all types of striatal projection neurons analyzed. Glutamic acid decarboxylase 67-, preproenkephalin-, and preprotachykinin A- but not prodynorphin-expressing neurons were protected by grafting of NT-3- or NT-4/5-secreting cells but with less efficiency than the BDNF-secreting cells. Our findings show that neurotrophins are able to promote the survival of striatal projection neurons in vivo and suggest that BDNF might be beneficial for the treatment of striatonigral degenerative disorders, including Huntington's disease.