Neuropharmacology

QPS Austria Scientist Publishes on L-type calcium channel blockers and substance P induction of cortical angiogenesis associated with beta-amyloid plaques in AD mice

It is well established that L-type calcium channels (LTCCs) are expressed in astroglia. However, their functional role is still speculative, especially under pathologic conditions. The aim of this study was to examine the cellular expression of all LTCC subunits around beta-amyloid plaques by in situ hybridization using 35S-labeled oligonucleotides.

The data show that messenger RNAs (mRNAs) of the LTCC CaV1.2 α1 subunit as well as all auxiliary β and α2δ subunits, except α2δ-4, were expressed in the hippocampus of age-matched wild-type mice. An unexpected finding was that cells directly located in the plaque core in the cortex expressed mRNAs for CaV1.2 α1, β2, β4, and α2δ-1, whereas no expression was detected in the halo. Furthermore, cells in the plaque core also expressed preprotachykinin-A mRNA, the precursor for substance P.

Confocal microscopy demonstrated that collagen-IV-stained brain vessels in the cortex were associated with the plaque core and were immunoreactive for substance P. In cortical organotypic brain slices of adult Alzheimer mice, LTCC blockers were shown to increase angiogenesis, which was further potentiated by substance P. In conclusion, the data show that brain vessels associated with beta-amyloid plaques express substance P and an LTCC, and may play a role in angiogenesis.

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