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Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and beta-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain.
Int J Dev Neurosci 2009; 27(6):517-23IJ

Abstract

The up-regulation of the angiogenic vascular endothelial growth factor (VEGF) in brains of Alzheimer patients in close relationship to beta-amyloid (Abeta) plaques, suggests a link of VEGF action and processing of the amyloid precursor protein (APP). To reveal whether VEGF may affect APP processing, brain slices derived from 17-month-old transgenic Tg2576 mice were exposed with 1ng/ml VEGF for 6, 24, and 72h, followed by assessing cytosolic and membrane-bound APP expression, level of both soluble and fibrillar Abeta-peptides, as well as activities of alpha- and beta-secretases in brain slice tissue preparations. Treatment of brain slices with VEGF did not significantly affect the expression level of APP, regardless of the exposure time studied. In contrast, VEGF exposure of brain slices for 6h reduced the formation of soluble, SDS extractable Abeta(1-40) and Abeta(1-42) as compared to brain slice cultures incubated in the absence of any drug, while the fibrillar Abeta peptides did not change significantly. This effect was less pronounced 24h after VEGF exposure, but was no longer detectable when brain slices were exposed by VEGF for 72h, which indicates an adaptive response to chronic VEGF exposure. The VEGF-mediated reduction in Abeta formation was accompanied by a transient decrease in beta-secretase activity peaking 6h after VEGF exposure. To reveal whether the VEGF-induced changes in soluble Abeta-level may be due to actions of VEGF on Abeta fibrillogenesis, the fibrillar status of Abeta was examined using the thioflavin-T binding assay. Incubation of Abeta preparations obtained from Tg2576 mouse brain cortex, in the presence of VEGF slightly decreased the fibrillar content with increasing incubation time up to 72h. The data demonstrate that VEGF may affect APP processing, at least in vitro, suggesting a role of VEGF in the pathogenesis of Alzheimer's disease.

Authors+Show Affiliations

Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19589380

Citation

Bürger, Susanne, et al. "Vascular Endothelial Growth Factor (VEGF) Affects Processing of Amyloid Precursor Protein and Beta-amyloidogenesis in Brain Slice Cultures Derived From Transgenic Tg2576 Mouse Brain." International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience, vol. 27, no. 6, 2009, pp. 517-23.
Bürger S, Noack M, Kirazov LP, et al. Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and beta-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain. Int J Dev Neurosci. 2009;27(6):517-23.
Bürger, S., Noack, M., Kirazov, L. P., Kirazov, E. P., Naydenov, C. L., Kouznetsova, E., ... Schliebs, R. (2009). Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and beta-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain. International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience, 27(6), pp. 517-23. doi:10.1016/j.ijdevneu.2009.06.011.
Bürger S, et al. Vascular Endothelial Growth Factor (VEGF) Affects Processing of Amyloid Precursor Protein and Beta-amyloidogenesis in Brain Slice Cultures Derived From Transgenic Tg2576 Mouse Brain. Int J Dev Neurosci. 2009;27(6):517-23. PubMed PMID: 19589380.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and beta-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain. AU - Bürger,Susanne, AU - Noack,Monika, AU - Kirazov,Ludmil P, AU - Kirazov,Evgeni P, AU - Naydenov,Cyrill L, AU - Kouznetsova,Elena, AU - Yafai,Yousef, AU - Schliebs,Reinhard, Y1 - 2009/07/07/ PY - 2009/04/28/received PY - 2009/06/12/revised PY - 2009/06/30/accepted PY - 2009/7/11/entrez PY - 2009/7/11/pubmed PY - 2009/11/17/medline SP - 517 EP - 23 JF - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience JO - Int. J. Dev. Neurosci. VL - 27 IS - 6 N2 - The up-regulation of the angiogenic vascular endothelial growth factor (VEGF) in brains of Alzheimer patients in close relationship to beta-amyloid (Abeta) plaques, suggests a link of VEGF action and processing of the amyloid precursor protein (APP). To reveal whether VEGF may affect APP processing, brain slices derived from 17-month-old transgenic Tg2576 mice were exposed with 1ng/ml VEGF for 6, 24, and 72h, followed by assessing cytosolic and membrane-bound APP expression, level of both soluble and fibrillar Abeta-peptides, as well as activities of alpha- and beta-secretases in brain slice tissue preparations. Treatment of brain slices with VEGF did not significantly affect the expression level of APP, regardless of the exposure time studied. In contrast, VEGF exposure of brain slices for 6h reduced the formation of soluble, SDS extractable Abeta(1-40) and Abeta(1-42) as compared to brain slice cultures incubated in the absence of any drug, while the fibrillar Abeta peptides did not change significantly. This effect was less pronounced 24h after VEGF exposure, but was no longer detectable when brain slices were exposed by VEGF for 72h, which indicates an adaptive response to chronic VEGF exposure. The VEGF-mediated reduction in Abeta formation was accompanied by a transient decrease in beta-secretase activity peaking 6h after VEGF exposure. To reveal whether the VEGF-induced changes in soluble Abeta-level may be due to actions of VEGF on Abeta fibrillogenesis, the fibrillar status of Abeta was examined using the thioflavin-T binding assay. Incubation of Abeta preparations obtained from Tg2576 mouse brain cortex, in the presence of VEGF slightly decreased the fibrillar content with increasing incubation time up to 72h. The data demonstrate that VEGF may affect APP processing, at least in vitro, suggesting a role of VEGF in the pathogenesis of Alzheimer's disease. SN - 1873-474X UR - https://www.unboundmedicine.com/medline/citation/19589380/Vascular_endothelial_growth_factor__VEGF__affects_processing_of_amyloid_precursor_protein_and_beta_amyloidogenesis_in_brain_slice_cultures_derived_from_transgenic_Tg2576_mouse_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0736-5748(09)00105-1 DB - PRIME DP - Unbound Medicine ER -