Platelet-derived growth factor exerts trophic effects on rat striatal DARPP-32-containing neurons in culture

Abstract

The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat strial neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF-BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.