Author/Editor     Žižek, Metka
Title     Trofični učinki glijalnega rastnega dejavnika na dopaminergične nevrone substance nigre pri podgani
Type     monografija
Place     Ljubljana
Publisher     Medicinska fakulteta
Publication year     2002
Volume     str. 57
Language     slo
Abstract     Absence of effective means for prevention or reversal of neurodegenerative processes that are a major element of morbidity in the elderly population are a constant insentive for research of new treatment options. Among other strategies, intraparenchymal administration of trophic substances into the diseased brain has already entered the stage of clinical safety trials. At the same time, basic science still does not have sufficient insight into the mechanisms of action of these substances or their possible side effects. Thus the aim of this study has been to address some of the unknown issues related to glial cellderived neurotrophic factor, GDNF, that is already being tested in clinic. The study evaluated major effects of intraparenchymal administration of rat recombinant GDNF on the rat nigrostriatal connections in vivo. Also, an excitotoxic injury of the parenchymum was employed to stimulate an increase in GDNF content and midterm effects of this procedure on the rat nigrostiatal connections was studied. In the preliminary study, the optimal parameters for exogenous GDNF administration and for stimulating its local availability were determined, based on changes these procedures had on (1) the number of dopaminergic (Da) neurons in the selected region of the substantia nigra (SN), (2) the average area size of the Da neurons in the SN, and (3) the density of Da innervation of the striatum. In the subsequent study, the research focused on the number of Da neurons of the SN as the major indicator of trofic effects of exogenous or endogenous GDNF. The study results showed that low dose rat recombinant (GDNF) administered into the infact rat nigrostriatal system has predominantly local effects, increasing the density of striatal Da innervation when administered intrastriatally and slightly increasing the number of Da neurons in the SN when administered perinigrally. (Abstract truncated at 2000 characters).
Descriptors     SUBSTANTIA NIGRA
GLIAL FIBRILLARY ACIDIC PROTEIN
CORPUS STRIATUM
NEURONS
DOPAMINE
QUINOLINIC ACID
IMMUNOHISTOCHEMISTRY
BLOTTING, WESTERN
APOPTOSIS
RATS, WISTAR