Short- and Long-Term Treatment of Mouse Cortical Primary Astrocytes with β-Amyloid Differentially Regulates the mRNA Expression of L-Type Calcium Channels

Abstract

Background: It is well established that reactive astrocytes express L-type calcium channels (LTCC), but their functional role is completely unknown. We have recently shown that reactive astrocytes highly express the Ca V 1.2 α 1-subunit around β-amyloid (Aβ) plaques in an Alzheimer mouse model. The aim of the present study was to explore whether Aβ peptides may regulate the mRNA expression of all LTCC subunits in primary mouse astrocytes in culture. Methods: Confluent primary astrocytes were incubated with 10 µg/ml of human or murine Aβ or the toxic fragment Aβ 25-35 for 3 days or for 3 weeks. The LTCC subunits were determined by quantitative RT-PCR. Results: Our data show that murine Aβ 42 slightly but significantly increased Ca V 1.2 and Ca V 1.3 expression when incubated for 3 days. This acute treatment with murine Aβ enhanced β 2 and β 3 mRNA levels but decreased α 2 δ-2 mRNA expression. When astrocytes were incubated for 3 weeks, the levels of Ca V 1.2 α 1 were significantly decreased by the murine Aβ and the toxic fragment. As a control, the protein kinase C-ε activator DCP-LA displayed a decrease in Ca V 2.1 expression. Conclusion: In conclusion, our data show that Aβ can differentially regulate LTCC expression in primary mouse astrocytes depending on incubation time.