title: L-type calcium channel blockers and substance P induce angiogenesis of cortical vessels associated with beta-amyloid plaques in an Alzheimer mouse model.
abstract: 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. We recently showed that the α1 subunit-like immunoreactivity of the CaV1.2 channel is strongly expressed in reactive astrocytes around beta-amyloid plaques in 11-month-old Alzheimer transgenic (tg) mice with the amyloid precursor protein London and Swedish mutations. The aim of the present study was to examine the cellular expression of all LTCC subunits around beta-amyloid plaques by in situ hybridization using (35)S-labeled oligonucleotides. Our 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. It was unexpected to see, 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. By means of confocal microscopy, we 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, we could demonstrate that LTCC blockers increased angiogenesis, which was further potentiated by substance P. In conclusion, our data show that brain vessels associated with beta-amyloid plaques express substance P and an LTCC and may play a role in angiogenesis.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Clinic of General and Social Psychiatry, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Daschil
authors.affiliation: Department of Psychiatry and Psychotherapy, University Clinic of General and Social Psychiatry, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Kathrin M
authors.initials: KM
authors.lastname: Kniewallner
authors.affiliation: Department of Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.affiliation: QPS Austria GmbH, Grambach, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
authors.affiliation: NeuroScios GmbH, Graz, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.affiliation: Department of Psychiatry and Psychotherapy A, General Hospital LKH Hall, Hall, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Marksteiner
authors.affiliation: Department of Psychiatry and Psychotherapy, University Clinic of General and Social Psychiatry, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: christian.humpel@i-med.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism; D004195:Disease Models, Animal; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics; D058225:Plaque, Amyloid / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013373:Substance P / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D013373:Substance P
keywords: Alzheimer; Angiogenesis; Beta-amyloid plaque; L-type calcium channel; Reactive astrocytes; Substance P; Vessels