Environmental Enrichment Counteracts Alzheimer's Neurovascular Dysfunction in TgCRND8 Mice

Overview

Journal Brain Pathol

Date 2007 Oct 11

PMID 17924982

Citations 36

Authors

Arne Herring

Hamzah Yasin

Oliver Ambree

Norbert Sachser

Werner Paulus

Kathy Keyvani

Affiliations

Soon will be listed here.

Abstract

We and others have recently demonstrated that cognitive and physical stimulation in form of environmental enrichment reduces cerebral beta-amyloid (Abeta) deposition in transgenic mouse models of Alzheimer's disease. This effect was independent from amyloid precursor protein (APP) expression or processing and rather a consequence of enhanced clearance of Abeta. However, the detailed mechanisms remain unclear. In the present study, we show that environmental enrichment in TgCRND8 mice (carrying human APP(Swedish+Indiana)) affect the neurovascular unit by increased angiogenesis and differential regulation of Abeta receptor/transporter molecules, namely up-regulation of LRP1, ApoE and A2M as well as down-regulation of RAGE so that brain to blood Abeta clearance is facilitated. These results suggest a hitherto unknown effect of environmental enrichment counteracting the vascular dysfunction in Alzheimer diseased brain.

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References

Bell R, Sagare A, Friedman A, Bedi G, Holtzman D, Deane R . Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system. J Cereb Blood Flow Metab. 2006; 27(5):909-18. PMC: 2853021. DOI: 10.1038/sj.jcbfm.9600419. View

Costa D, Cracchiolo J, Bachstetter A, Hughes T, Bales K, Paul S . Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms. Neurobiol Aging. 2006; 28(6):831-44. DOI: 10.1016/j.neurobiolaging.2006.04.009. View

Hayashi S, Asahara T, Masuda H, Isner J, Losordo D . Functional ephrin-B2 expression for promotive interaction between arterial and venous vessels in postnatal neovascularization. Circulation. 2005; 111(17):2210-8. DOI: 10.1161/01.CIR.0000163566.07427.73. View

Park Y, Kang Y, Butterfield J, Detmar M, Goronzy J, Weyand C . Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis. Am J Pathol. 2004; 165(6):2087-98. PMC: 1618704. DOI: 10.1016/S0002-9440(10)63259-2. View

Zlokovic B, Martel C, Matsubara E, McComb J, Zheng G, McCluskey R . Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Proc Natl Acad Sci U S A. 1996; 93(9):4229-34. PMC: 39517. DOI: 10.1073/pnas.93.9.4229. View

Jankowsky J, Melnikova T, Fadale D, Xu G, Slunt H, Gonzales V . Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. J Neurosci. 2005; 25(21):5217-24. PMC: 4440804. DOI: 10.1523/JNEUROSCI.5080-04.2005. View

Pan W, Kastin A, Zankel T, van Kerkhof P, Terasaki T, Bu G . Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier. J Cell Sci. 2004; 117(Pt 21):5071-8. DOI: 10.1242/jcs.01381. View

Deane R, Wu Z, Sagare A, Davis J, Yan S, Hamm K . LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron. 2004; 43(3):333-44. DOI: 10.1016/j.neuron.2004.07.017. View

Black J, Isaacs K, Anderson B, Alcantara A, Greenough W . Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Natl Acad Sci U S A. 1990; 87(14):5568-72. PMC: 54366. DOI: 10.1073/pnas.87.14.5568. View

10.

Chishti M, Yang D, Janus C, Phinney A, Horne P, Pearson J . Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem. 2001; 276(24):21562-70. DOI: 10.1074/jbc.M100710200. View

11.

Tanzi R, Moir R, Wagner S . Clearance of Alzheimer's Abeta peptide: the many roads to perdition. Neuron. 2004; 43(5):605-8. DOI: 10.1016/j.neuron.2004.08.024. View

12.

Arendash G, Garcia M, Costa D, Cracchiolo J, Wefes I, Potter H . Environmental enrichment improves cognition in aged Alzheimer's transgenic mice despite stable beta-amyloid deposition. Neuroreport. 2004; 15(11):1751-4. DOI: 10.1097/01.wnr.0000137183.68847.4e. View

13.

Friedland R, Fritsch T, Smyth K, Koss E, Lerner A, Chen C . Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci U S A. 2001; 98(6):3440-5. PMC: 30672. DOI: 10.1073/pnas.061002998. View

14.

Boucher P, Gotthardt M, Li W, Anderson R, Herz J . LRP: role in vascular wall integrity and protection from atherosclerosis. Science. 2003; 300(5617):329-32. DOI: 10.1126/science.1082095. View

15.

Lazarov O, Robinson J, Tang Y, Hairston I, Korade-Mirnics Z, Lee V . Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell. 2005; 120(5):701-13. DOI: 10.1016/j.cell.2005.01.015. View

16.

Naiche L, Papaioannou V . Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois. Development. 2003; 130(12):2681-93. DOI: 10.1242/dev.00504. View

17.

Goldin A, Beckman J, Schmidt A, Creager M . Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006; 114(6):597-605. DOI: 10.1161/CIRCULATIONAHA.106.621854. View

18.

Donahue J, Flaherty S, Johanson C, Duncan 3rd J, Silverberg G, Miller M . RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease. Acta Neuropathol. 2006; 112(4):405-15. DOI: 10.1007/s00401-006-0115-3. View

19.

Zlokovic B . Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci. 2005; 28(4):202-8. DOI: 10.1016/j.tins.2005.02.001. View

20.

Casella G, Marcillo A, Bunge M, Wood P . New vascular tissue rapidly replaces neural parenchyma and vessels destroyed by a contusion injury to the rat spinal cord. Exp Neurol. 2002; 173(1):63-76. DOI: 10.1006/exnr.2001.7827. View