PDGF-BB exerts trophic activity on cultured GABA interneurons from the newborn rat cerebellum.
Platelet-derived growth factor (PDGF) is a well known mitogen for mesenchyme-derived cells and glial cells. Its presence in neuronal cells of the central nervous system has only recently been described. We have shown earlier that neurons of newborn rat brains in culture express PDGF beta-receptors and that PDGF-BB, a homodimer of PDGF B-chain, increases survival and promotes neurite outgrowth of newborn cerebellar cells (Smits et al., Proc. Natl Acad. Sci. USA, 88, 8159-8163, 1991). In this study, the effects of PDGF on early postnatal rat cerebellar cells were further explored. By using chemically defined serum-free medium, we have established primary cell cultures of rat cerebella (postnatal day 4-5) containing 70-80% neuronal cells. During the first 10 days in vitro, no difference in total cell number was found between PDGF-BB-treated and untreated cultures. After this time period, however, increased survival of the PDGF-BB-treated cells was found. Within the first 10 days in vitro, the addition of PDGF-BB to the cultures resulted in a relative increase in survival of interneurons expressing glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. Moreover, addition of PDGF-BB in the untreated cell culture resulted in a rapid increase of GAD mRNA. These results show that PDGF-BB acts as a trophic factor on GABAergic interneurons of the cerebellum by up-regulating GAD synthesis and prolonging the survival of these cells. Furthermore, in situ hybridization revealed that there are scattered cells present in the early postnatal cerebellum that express PDGF beta-receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Smits
A
A
Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala, Sweden.
Ballagi
A E
AE
Funa
K
K
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D000077214:Becaplermin; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018076:DNA, Complementary; D015335:Molecular Probes; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077214:Becaplermin; D005680:gamma-Aminobutyric Acid; D017479:Receptors, Platelet-Derived Growth Factor; D005968:Glutamate Decarboxylase