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  • CaV1.2 calcium channel expression in reactive astrocytes is associated with the formation of amyloid-β plaques in an Alzheimer's disease mouse model.

CaV1.2 calcium channel expression in reactive astrocytes is associated with the formation of amyloid-β plaques in an Alzheimer's disease mouse model.

Journal of Alzheimer's disease : JAD (2013-08-21)
Nina Daschil, Gerald J Obermair, Bernhard E Flucher, Nadia Stefanova, Birgit Hutter-Paier, Manfred Windisch, Christian Humpel, Josef Marksteiner
ABSTRACT

Increased activity of L-type Ca2+ channels has been implicated in the pathogenesis of dementia and Alzheimer's disease (AD). Previously we detected CaV1.2 α1-subunit-positive expression in reactive astrocytes surrounding the plaques of 12 month-old transgenic mice overexpressing hAβPP751 with the London (V717I) and Swedish (K670M/N671L) mutations. Here we examined whether increased CaV1.2 α1-subunit expression precedes plaque formation or is specifically associated with the increased amyloid-β (Aβ) load in the plaques. Quantitative RT-PCR expression profiling of all high voltage-gated Ca2+ channel subunits (α1, β, and α2δ) revealed no difference in the hippocampi of 2, 4, and 11 month-old wild type (wt) and transgenic (tg) mice. Immunohistochemistry demonstrated that expression of CaV1.2 α1-subunit, but not of the auxiliary β4 Ca2+ channel subunit, specifically associated with Aβ-positive plaques in brains of 11 month tg mice. No difference in CaV1.2 α1-subunit labeling was found in 2 and 4 month-old wt and tg mice prior to plaque formation. The CaV1.2 α1-subunit-positive cells in 11 month-old tg mice also labeled with GFAP, but not with the microglia marker Iba1. In contrast, GFAP-positive cells induced by injection of quinolinic acid did not reveal any CaV1.2 α1-subunit immunoreactivity. Together these results indicate that the expression of CaV1.2 α1-subunits in reactive astrocytes in the tg AD mouse model is related to the increased amyloid-β load in the plaques rather than caused by effects on gene regulation or mechanisms preceding the manifestation of AD as seen by plaque formation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Calcium Channel (α1C Subunit) (L-type of Voltage-gated Ca2+ Channel) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein Antibody, Chemicon®, from chicken
Sigma-Aldrich
Anti-β-Amyloid (13-28) antibody, Mouse monoclonal, clone BAM90.1, purified from hybridoma cell culture