Protective effects of neurotrophin-4/5 and transforming growth factor- α on striatal neuronal phenotypic degeneration after excitotoxic lesioning with quinolinic acid

• Published in: Neuroscience 1997-05, Vol.78 (1), p.73-86
• Main Authors: Alexi, T, Venero, J.L, Hefti, F
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; calbindin; Calcium-Binding Proteins - metabolism; calretinin; Cell Count; Choline O-Acetyltransferase - metabolism; Female; GABAergic; Glutamate Decarboxylase - metabolism; Huntington's disease; Immunohistochemistry; Medical sciences; NADPH Dehydrogenase - metabolism; Neostriatum - cytology; Neostriatum - drug effects; Neostriatum - enzymology; Nerve Degeneration - drug effects; Nerve Growth Factors - pharmacology; Neurons - drug effects; Neurons - enzymology; Neurons - physiology; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - pharmacology; neurotrophic factor; parvalbumin; Pharmacology. Drug treatments; Phenotype; Quinolinic Acid - toxicity; Rats; Rats, Wistar; Transforming Growth Factor alpha - pharmacology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(97)83046-1

Lesioning of the mammalian striatum with the excitotoxin quinolinic acid results in a pattern of neuropathology that resembles that of post mortem Huntington's disease brain. Certain neurotrophic factors can rescue degenerating cells in a variety of lesion types, including those produced by neurotoxins. Several neurotrophic factors promote the survival of striatal neurons and/or are localized within the striatum. Of these factors, neurotrophin-4/5 and transforming growth factor- α were chosen for administration to rats lesioned with quinolinic acid. Adult rats received a single unilateral intrastriatal injection of quinolinic acid (120 nmol) and either trophic factors or the control protein cytochrome c for seven days thereafter. The pattern of phenotypic degeneration was assessed by immunocytochemical labeling of various striatal neuronal populations at five rostrocaudal levels. Quinolinic acid produced a preferential loss in the number of cells immunoreactive for glutamate decarboxylase, with a relative sparing of the number of choline acetyltransferase-immunoreactive cells and, to a lesser degree, calretinin-immunoreactive cells. None of these phenotypic populations was protected by either neurotrophin-4/5 or transforming growth factor- α. In contrast, when glutamate decarboxylase cells were alternatively identified by calbindin immunolabeling, both factors were found to have partially reversed the loss in the number of calbindin-positive cells induced by excitolesioning. In addition, the loss in the number of parvalbumin-immunopositive cells due to quinolinic acid was partially reversed by neurotrophin-4/5, while the loss in the number of NADPH-diaphorase-stained cells was partially reversed by transforming growth factor- α. These findings reveal a new population of striatal cells, calretinin neurons, that are relatively resistant to quinolinic acid toxicity and that neurotrophin-4/5 and transforming growth factor- α partially protect against the phenotypic degeneration of striatal cell populations in an in vivo animal model of Huntington's disease.