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PDGF-BB exerts trophic activity on cultured GABA interneurons from the newborn rat cerebellum
1Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala, Sweden.
Insights
Platelet-derived growth factor-BB (PDGF-BB) supports the survival of cerebellar GABAergic interneurons. This growth factor increases the synthesis of glutamic acid decarboxylase (GAD) and prolongs the lifespan of these crucial neuronal cells.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Platelet-derived growth factor (PDGF) is a known mitogen for various cell types.
- Recent findings indicate PDGF's presence in central nervous system neurons.
- Previous studies showed PDGF-BB promotes survival and neurite outgrowth in cerebellar cells.
Purpose of the Study:
- To investigate the specific effects of PDGF on early postnatal rat cerebellar cells.
- To determine if PDGF acts as a trophic factor for specific neuronal populations.
- To explore PDGF's influence on GABAergic interneuron survival and function.
Main Methods:
- Primary cell cultures of rat cerebella (postnatal day 4-5) were established in chemically defined serum-free medium.
- Cell cultures were treated with PDGF-BB and compared to untreated controls.
- Cell survival, cell numbers, and glutamic acid decarboxylase (GAD) mRNA levels were analyzed.
- In situ hybridization was used to detect PDGF beta-receptor mRNA expression.
Main Results:
- PDGF-BB treatment led to increased survival of cerebellar cells after 10 days in vitro.
- A relative increase in the survival of interneurons expressing GAD was observed with PDGF-BB.
- PDGF-BB significantly increased GAD mRNA levels in the cell cultures.
- Scattered cells expressing PDGF beta-receptor mRNA were identified in the early postnatal cerebellum.
Conclusions:
- PDGF-BB functions as a trophic factor for cerebellar GABAergic interneurons.
- PDGF-BB up-regulates GAD synthesis and prolongs the survival of these interneurons.
- These findings highlight PDGF's role in the development and maintenance of specific neuronal populations in the cerebellum.
Abstract:
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)