Short- and long-term treatment of mouse cortical primary astrocytes with β-amyloid differentially regulates the mRNA expression of L-type calcium channels.

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 CaV1.2 α1-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. Confluent primary astrocytes were incubated with 10 µg/ml of human or murine Aβ or the toxic fragment Aβ25-35 for 3 days or for 3 weeks. The LTCC subunits were determined by quantitative RT-PCR. Our data show that murine Aβ42 slightly but significantly increased CaV1.2 and CaV1.3 expression when incubated for 3 days. This acute treatment with murine Aβ enhanced β2 and β3 mRNA levels but decreased α2δ-2 mRNA expression. When astrocytes were incubated for 3 weeks, the levels of CaV1.2 α1 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 CaV2.1 expression. In conclusion, our data show that Aβ can differentially regulate LTCC expression in primary mouse astrocytes depending on incubation time.