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In vitro hormonal regulation of astrocyte proliferation
Abstract:
Previously, we showed that purified myelin basic protein (MBP) induces a two-fold increase in the proliferation rate of astrocytes in culture. This observation allowed us to hipothesize that MBP-induced astroglial proliferation might be one of the causes of astrogliosis and astroglial scar formation in case of in vivo myelin breakdown. Also, we observed that dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) reduce the amount of 3H-Thymidine incorporated by cultured astrocytes. In the present study, we investigated by a combined 3H-Thymidine autoradiography/immunocytochemistry technique whether the mitogenic effect that MBP exerts upon astrocytes in vitro can be prevented by DHEA and DHEA-S. Results showed that a treatment of the cells with MBP only induces approximately a two-fold increase in the number of silver grains overlaying the nuclei of astrocytes. In cultures treated with both MBP and DHEA there was a 2.5-3 fold reduction in the number of silver grains, while DHEA-S provoked a 3-4 fold reduction. These results allow us to speculate that DHEA and DHEA-S could modulate the astrogliosis that usually accompanies myelin breakdown.
Insights
Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) can prevent myelin basic protein (MBP)-induced astrocyte proliferation. These findings suggest DHEA and DHEA-S may modulate astrogliosis during myelin breakdown.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Myelin basic protein (MBP) is known to increase astrocyte proliferation in vitro.
- This proliferation is hypothesized to contribute to astrogliosis and glial scar formation following in vivo myelin breakdown.
- Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) have been observed to reduce astrocyte proliferation.
Purpose of the Study:
- To investigate if DHEA and DHEA-S can prevent the mitogenic effect of MBP on astrocytes in vitro.
- To quantify the effect of DHEA and DHEA-S on MBP-induced astrocyte proliferation.
Main Methods:
- Combined 3H-Thymidine autoradiography and immunocytochemistry techniques were employed.
- Primary astrocyte cultures were treated with MBP alone, or in combination with DHEA or DHEA-S.
- Proliferation was assessed by quantifying silver grains over astrocyte nuclei.
Main Results:
- MBP treatment alone resulted in a two-fold increase in astrocyte proliferation.
- Co-treatment with MBP and DHEA reduced the number of silver grains by 2.5-3 fold.
- Co-treatment with MBP and DHEA-S reduced the number of silver grains by 3-4 fold.
Conclusions:
- DHEA and DHEA-S significantly inhibit MBP-induced astrocyte proliferation in vitro.
- These findings suggest a potential role for DHEA and DHEA-S in modulating astrogliosis associated with myelin breakdown.