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

• Published in: Journal of neurochemistry Vol. 75; no. 5; pp. 2190 - 2199
• Main Authors: Pérez‐Navarro, Esther, Canudas, Anna M., Åkerud, Peter, Alberch, Jordi, Arenas, Ernest
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01-11-2000; Blackwell
• Subjects: Animals; Biological and medical sciences; Brain-Derived Neurotrophic Factor - biosynthesis; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Cell Death - drug effects; Cell Line; Cell Transplantation; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Enkephalins - biosynthesis; Fibroblasts - metabolism; Fibroblasts - transplantation; Glutamate Decarboxylase - biosynthesis; Grafting; Huntington Disease - drug therapy; Huntington Disease - metabolism; Huntington Disease - pathology; Isoenzymes - biosynthesis; Male; Medical sciences; Medicin och hälsovetenskap; Nerve Growth Factors - biosynthesis; Nerve Growth Factors - pharmacology; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neurotrophin 3 - biosynthesis; Neurotrophin 3 - pharmacology; Phosphorylation - drug effects; Protein Precursors - biosynthesis; Quinolinate; Quinolinic Acid; Rat striatum; Rats; Rats, Inbred F344; Receptor, trkB - metabolism; Survival; Tachykinins - biosynthesis; Neurotrophin; Animal model; Nervous system diseases; Rat; Rodentia; Central nervous system; Huntington disease; Basal ganglion; Corpus striatum; Survival; Cerebral disorder; Genetic disease; Vertebrata; Experimental disease; Mammalia; Central nervous system disease; Graft; Degenerative disease; Brain derived neurotrophic factor; Extrapyramidal syndrome
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0752190.x

: 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.