Nerve growth factor and basic fibroblast growth factor protect cholinergic neurons against quinolinic acid excitotoxicity in rat neostriatum.
In the present work we have characterized a possible mechanism leading to the early survival of neostriatal cholinergic neurons after quinolinic acid injection. Different doses of quinolinic acid were injected in rat neostriatum and two different parameters were analysed 7 days after the lesion: choline acetyltransferase (ChAT) activity and nerve growth factor (NGF) levels. We have observed that ChAT activity decreased (until 68 nmol quinolinic acid) and NGF levels increased (until 34 nmol quinolinic acid) in a dose-dependent manner. In order to characterize the time-course of the lesion on NGF levels and ChAT activity, and the possible protective effect of NGF and basic fibroblast growth factor (bFGF) on cholinergic neurons, we have used the quinolinic acid dose (68 nmol) at which the first decrease of ChAT activity was observed. ChAT activity and NGF levels showed different patterns of response to quinolinic acid injection, since the maximal effect was reached at 1 day for ChAT activity and at 2 days for NGF levels. NGF or bFGF simultaneously injected with quinolinic acid (68 nmol) completely prevented the decrease in ChAT activity in a dose-dependent manner but NGF was more effective than bFGF. Furthermore, differences observed in ChAT activity after NGF but not bFGF treatment were correlated with changes in the number of ChAT immunoreactive cells. Finally, we have also observed that, although bFGF alone was not able to modify NGF levels, bFGF simultaneously injected with quinolinic acid produced an increase of NGF levels higher than that observed after quinolinic acid injection alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Pérez-Navarro
E
E
Departament de Biologia Cel.lular i Anatomia Patològica, Hospital de Bellvitge, Facultat de Medicina, Universitat de Barcelona, Spain.
Alberch
J
J
Arenas
E
E
Calvo
N
N
Marsal
J
J
D000818:Animals; D002470:Cell Survival; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D002795:Choline O-Acetyltransferase; D017378:Quinolinic Acid