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PMID: 16687490 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 26 ·No. 19 ·2006-05-10 ·Pages 4985-94

Xu Q, Bernardo A, Walker D, Kanegawa T, Mahley RW, Huang Y

Abstract

To study the profile and regulation of apolipoprotein E (apoE) expression in the CNS, we generated mice in which apoE expression can be detected in vivo with unprecedented sensitivity and resolution. cDNA encoding enhanced green fluorescent protein (EGFP) with a stop codon was inserted by gene targeting into the apoE gene locus (EGFPapoE) immediately after the translation initiation site. Insertion of EGFP into one apoE allele provides a real-time location marker of apoE expression in vivo; the remaining allele is sufficient to maintain normal cellular physiology. In heterozygous EGFPapoE mice, EGFP was highly expressed in hepatocytes and peritoneal macrophages. EGFP was also expressed in brain astrocytes; however some astrocytes (approximately 25%) expressed no EGFP, suggesting that a subset of these cells does not express apoE. EGFP was expressed in <10% of microglia after kainic acid treatment, suggesting that microglia are not a major source of brain apoE. Although hippocampal neurons did not express EGFP under normal conditions, kainic acid treatment induced intense expression of EGFP in injured neurons, demonstrating apoE expression in neurons in response to excitotoxic injury. The neuronal expression was confirmed by in situ hybridization of mouse apoE mRNA and by anti-apoE immunostaining. Smooth muscle cells of large blood vessels and cells surrounding small vessels in the CNS also strongly expressed EGFP, as did cells in the choroid plexus. EGFPapoE reporter mice will be useful for studying the regulation of apoE expression in the CNS and might provide insights into the diverse mechanisms of apoE4-related neurodegeneration.

MeSH Terms
Animals Apolipoproteins E/genetics,metabolism Brain/metabolism Gene Expression Profiling Gene Expression Regulation/physiology Gene Targeting/methods Green Fluorescent Proteins/genetics,metabolism Mice Microscopy, Fluorescence/methods Neurons/metabolism
Chemicals
Apolipoproteins E Green Fluorescent Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xu Qin
Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA.
Bernardo Aubrey
Walker David
Kanegawa Tiffany
Mahley Robert W
Huang Yadong
References (107)
107 references, click to expand
  1. Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.
    J Neurosci. 2003 Aug 27;23(21):7889-96 PMID: 12944519
  2. Introduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11587-91 PMID: 11553788
  3. Apolipoprotein E alleles as risk factors in Alzheimer's disease.
    Annu Rev Med. 1996;47:387-400 PMID: 8712790
  4. Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.
    J Clin Invest. 1994 Aug;94(2):860-9 PMID: 8040342
  5. Expression of apolipoprotein E by cultured vascular smooth muscle cells is controlled by growth state.
    J Cell Biol. 1988 Sep;107(3):1207-13 PMID: 2458361
  6. Microglial apolipoprotein E and astroglial apolipoprotein J expression in vitro: opposite effects of lipopolysaccharide.
    J Neurochem. 2003 Jun;85(6):1455-67 PMID: 12787065
  7. Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study.
    J Neuropathol Exp Neurol. 1994 Sep;53(5):535-44 PMID: 8083695
  8. Genetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4103-8 PMID: 9108112
  9. Transforming growth factor-beta1-induced expression of smooth muscle marker genes involves activation of PKN and p38 MAPK.
    J Biol Chem. 2005 Sep 2;280(35):31172-81 PMID: 15980430
  10. Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice.
    J Neurosci. 2004 Mar 10;24(10):2527-34 PMID: 15014128
  11. Expression of apolipoprotein E in normal and diverse neurodegenerative disease brain.
    Neuroreport. 1996 Jul 29;7(11):1733-9 PMID: 8905654
  12. Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid beta.
    J Neurochem. 1997 Nov;69(5):1995-2004 PMID: 9349544
  13. ApoE deficiency compromises the blood brain barrier especially after injury.
    Mol Med. 2001 Dec;7(12):810-5 PMID: 11844869
  14. Apolipoprotein E, plaques, tangles and cholinergic dysfunction in Alzheimer's disease.
    Ann N Y Acad Sci. 1996 Jan 17;777:166-74 PMID: 8624080
  15. APOE epsilon 3/ epsilon 4 heterozygotes have an elevated proportion of apolipoprotein E4 in cerebrospinal fluid relative to plasma, independent of Alzheimer's disease diagnosis.
    Exp Neurol. 2003 Sep;183(1):249-53 PMID: 12957508
  16. Lipoprotein(A): physiologic function, association with atherosclerosis, and effects of lipid-lowering drug therapy.
    Ann Pharmacother. 1994 Mar;28(3):343-51 PMID: 8193425
  17. Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins.
    Brain Res. 2002 Dec 20;958(1):100-11 PMID: 12468034
  18. Apolipoprotein E4 potentiates amyloid beta peptide-induced lysosomal leakage and apoptosis in neuronal cells.
    J Biol Chem. 2002 Jun 14;277(24):21821-8 PMID: 11912196
  19. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.
    J Clin Invest. 1985 Oct;76(4):1501-13 PMID: 3932467
  20. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.
    JAMA. 1997 Oct 22-29;278(16):1349-56 PMID: 9343467
  21. Kainic acid induced seizures: neurochemical and histopathological changes.
    Neuroscience. 1983 Dec;10(4):1301-15 PMID: 6141539
  22. Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease.
    Am J Pathol. 1998 Sep;153(3):725-33 PMID: 9736023
  23. Familial Alzheimer disease among Caribbean Hispanics: a reexamination of its association with APOE.
    Arch Neurol. 2002 Jan;59(1):87-91 PMID: 11790235
  24. Impairment of the blood-nerve and blood-brain barriers in apolipoprotein e knockout mice.
    Exp Neurol. 2001 May;169(1):13-22 PMID: 11312553
  25. Neurons of the human frontal cortex display apolipoprotein E immunoreactivity: implications for Alzheimer's disease.
    J Neuropathol Exp Neurol. 1996 Mar;55(3):372-80 PMID: 8786396
  26. Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction.
    Stroke. 2003 Apr;34(4):875-80 PMID: 12649507
  27. Apolipoprotein E and cognitive performance.
    Nature. 2000 Mar 23;404(6776):352-4 PMID: 10746713
  28. Embryonic stem cells can form germ cells in vitro.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11457-62 PMID: 14504407
  29. ApoE immunoreactivity and microglial cells in Alzheimer's disease brain.
    Neurosci Lett. 1995 Jul 28;195(1):5-8 PMID: 7478253
  30. Isoform-specific binding of apolipoprotein E to beta-amyloid.
    J Biol Chem. 1994 Sep 23;269(38):23403-6 PMID: 8089103
  31. Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology.
    Exp Neurol. 2001 Aug;170(2):326-44 PMID: 11476599
  32. The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics.
    JAMA. 1998 Mar 11;279(10):751-5 PMID: 9508150
  33. Neuronal apolipoprotein E is not synthesized in neuron after focal ischemia in rat brain.
    Neurol Res. 2003 Jun;25(4):390-4 PMID: 12870266
  34. Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes.
    J Virol. 1991 Sep;65(9):4759-68 PMID: 1870200
  35. Astrocytes down-regulate neuronal beta-amyloid precursor protein expression and modify its processing in an apolipoprotein E isoform-specific manner.
    Eur J Neurosci. 2001 Jul;14(2):256-66 PMID: 11553277
  36. Transcription factor AP-2 regulates human apolipoprotein E gene expression in astrocytoma cells.
    J Neurosci. 1996 Dec 1;16(23):7550-6 PMID: 8922411
  37. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy.
    Ann Neurol. 1995 Aug;38(2):254-9 PMID: 7654074
  38. Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15233-8 PMID: 10611368
  39. Synthesis and processing of apolipoprotein E in human brain cultures.
    Glia. 2001 Mar 15;33(4):298-305 PMID: 11246228
  40. Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning.
    Brain Res Mol Brain Res. 1991 Sep;11(2):97-106 PMID: 1661818
  41. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.
    Science. 1993 Aug 13;261(5123):921-3 PMID: 8346443
  42. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.
    Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8098-102 PMID: 8367470
  43. Hypomorphic apolipoprotein E mice: a new model of conditional gene repair to examine apolipoprotein E-mediated metabolism.
    J Biol Chem. 2002 Mar 29;277(13):11064-8 PMID: 11792702
  44. Expression of the human apolipoprotein E gene is regulated by multiple positive and negative elements.
    J Biol Chem. 1988 Jun 15;263(17):8300-8 PMID: 3372525
  45. L-serine-mediated release of apolipoprotein E and lipids from microglial cells.
    Exp Neurol. 2004 Feb;185(2):220-31 PMID: 14736503
  46. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain.
    J Biol Chem. 1987 Oct 15;262(29):14352-60 PMID: 3115992
  47. Astroglial regulation of apolipoprotein E expression in neuronal cells. Implications for Alzheimer's disease.
    J Biol Chem. 2004 Jan 30;279(5):3862-8 PMID: 14585838
  48. Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target.
    Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18700-5 PMID: 16344478
  49. Vascular apolipoprotein e expression and recruitment from circulation to modulate smooth muscle cell response to endothelial denudation.
    Am J Pathol. 2004 Jun;164(6):2109-16 PMID: 15161645
  50. Localization of a liver-specific enhancer in the apolipoprotein E/C-I/C-II gene locus.
    J Lipid Res. 1993 Oct;34(10):1699-707 PMID: 8245720
  51. Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain.
    J Biol Chem. 1996 Apr 5;271(14):8373-80 PMID: 8626535
  52. Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10966-71 PMID: 12939405
  53. The molecular pathology of Alzheimer's disease.
    Neuron. 1991 Apr;6(4):487-98 PMID: 1673054
  54. Dissociation of apolipoprotein and apolipoprotein receptor response to lesion in the rat brain: an in situ hybridization study.
    Neuroscience. 1998 Aug;85(4):1161-71 PMID: 9681954
  55. Hepatocyte-derived ApoE is more effective than non-hepatocyte-derived ApoE in remnant lipoprotein clearance.
    J Biol Chem. 2003 Mar 28;278(13):11670-5 PMID: 12551940
  56. Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase: modulation by zinc.
    J Biol Chem. 2004 Oct 22;279(43):44795-801 PMID: 15322121
  57. Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model.
    J Neurosci. 2005 Mar 16;25(11):2803-10 PMID: 15772340
  58. Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration.
    J Neurosci. 1999 Jun 15;19(12):4867-80 PMID: 10366621
  59. Apolipoprotein E expression by neurons surviving excitotoxic stress.
    Neurobiol Dis. 1999 Dec;6(6):508-14 PMID: 10600406
  60. Evolutionary duplication of a hepatic control region in the human apolipoprotein E gene locus. Identification of a second region that confers high level and liver-specific expression of the human apolipoprotein E gene in transgenic mice.
    J Biol Chem. 1995 Nov 3;270(44):26278-81 PMID: 7592836
  61. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
    Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9649-53 PMID: 8415756
  62. Androgens protect against apolipoprotein E4-induced cognitive deficits.
    J Neurosci. 2002 Jun 15;22(12):5204-9 PMID: 12077215
  63. Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E.
    J Lipid Res. 1999 Jan;40(1):1-16 PMID: 9869645
  64. LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP.
    Curr Alzheimer Res. 2005 Apr;2(2):269-73 PMID: 15974929
  65. The choroid plexus removes beta-amyloid from brain cerebrospinal fluid.
    Exp Biol Med (Maywood). 2005 Nov;230(10):771-6 PMID: 16246905
  66. Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
    Am J Pathol. 1994 Nov;145(5):1030-5 PMID: 7977635
  67. Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice.
    J Biol Chem. 2002 Aug 16;277(33):29919-26 PMID: 12042316
  68. Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10914-9 PMID: 9724804
  69. ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo.
    Neuron. 2004 Jan 22;41(2):193-202 PMID: 14741101
  70. Purification of apolipoprotein E attenuates isoform-specific binding to beta-amyloid.
    J Biol Chem. 1995 Apr 21;270(16):9039-42 PMID: 7721816
  71. Two hepatic enhancers, HCR.1 and HCR.2, coordinate the liver expression of the entire human apolipoprotein E/C-I/C-IV/C-II gene cluster.
    J Biol Chem. 1997 Nov 14;272(46):29113-9 PMID: 9360987
  72. Expression of the apolipoprotein E gene in the skin is controlled by a unique downstream enhancer.
    J Invest Dermatol. 2001 Jan;116(1):77-84 PMID: 11168801
  73. Apolipoprotein E and Alzheimer disease.
    Neurology. 2006 Jan 24;66(2 Suppl 1):S79-85 PMID: 16432152
  74. Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord.
    Am J Pathol. 2000 Nov;157(5):1495-510 PMID: 11073810
  75. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid.
    Neurosci Lett. 1992 Feb 3;135(2):235-8 PMID: 1625800
  76. Specific regional transcription of apolipoprotein E in human brain neurons.
    Am J Pathol. 1999 Feb;154(2):601-11 PMID: 10027417
  77. Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity.
    Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18694-9 PMID: 16344479
  78. Sialylated human apolipoprotein E (apoEs) is preferentially associated with neuron-enriched cultures from APOE transgenic mice.
    Neurobiol Dis. 1999 Feb;6(1):63-75 PMID: 10078974
  79. Synthesis and regulation of apolipoprotein E during the differentiation of human neuronal precursor NT2/D1 cells into postmitotic neurons.
    Exp Neurol. 2000 Dec;166(2):415-21 PMID: 11085906
  80. Human apolipoprotein E2, E3, and E4 isoform-specific transgenic mice: human-like pattern of glial and neuronal immunoreactivity in central nervous system not observed in wild-type mice.
    Neurobiol Dis. 1996;3(3):229-45 PMID: 8980023
  81. The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia.
    J Clin Invest. 1999 Jan;103(2):291-9 PMID: 9916141
  82. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments.
    Nature. 1994 Nov 3;372(6501):92-4 PMID: 7969426
  83. Identification of a novel enhancer of brain expression near the apoE gene cluster by comparative genomics.
    Biochim Biophys Acta. 2004 Jan 5;1676(1):41-50 PMID: 14732489
  84. New frontiers in Alzheimer's disease genetics.
    Neuron. 2001 Oct 25;32(2):181-4 PMID: 11683989
  85. Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2892-7 PMID: 10694577
  86. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 PMID: 8446617
  87. ApoE synthesis in human neuroblastoma cells.
    Neurobiol Dis. 1997;4(5):356-64 PMID: 9440124
  88. Mouse macrophages synthesize and secrete a protein resembling apolipoprotein E.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7545-9 PMID: 6950395
  89. Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11836-41 PMID: 12923295
  90. Apolipoprotein E is upregulated in olfactory bulb glia following peripheral receptor lesion in mice.
    Exp Neurol. 2001 Nov;172(1):128-36 PMID: 11681846
  91. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease.
    Brain Res. 1991 Feb 8;541(1):163-6 PMID: 2029618
  92. Amyloid precursor proteins protect neurons of transgenic mice against acute and chronic excitotoxic injuries in vivo.
    Neuroscience. 1997 May;78(1):135-46 PMID: 9135095
  93. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.
    Neurology. 1993 Aug;43(8):1467-72 PMID: 8350998
  94. Choroid plexus, aging of the brain, and Alzheimer's disease.
    Front Biosci. 2003 May 01;8:s515-21 PMID: 12700093
  95. Duplicated downstream enhancers control expression of the human apolipoprotein E gene in macrophages and adipose tissue.
    J Biol Chem. 2000 Oct 13;275(41):31567-72 PMID: 10893248
  96. Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.
    Acta Neuropathol. 2000 Nov;100(5):451-8 PMID: 11045665
  97. Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease.
    J Mol Neurosci. 2004;23(3):189-204 PMID: 15181247
  98. Expression of the human apolipoprotein E gene in cultured mammalian cells.
    J Biol Chem. 1986 Jul 25;261(21):9858-64 PMID: 3733697
  99. Amyloid beta40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice.
    J Alzheimers Dis. 2001 Feb;3(1):23-30 PMID: 12214069
  100. Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8838-43 PMID: 11447277
  101. Regionally specific neuronal expression of human APOE gene in transgenic mice.
    Neurosci Lett. 1998 Apr 24;246(2):65-8 PMID: 9627181
  102. SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling.
    J Biol Chem. 2005 Dec 2;280(48):40364-74 PMID: 16183991
  103. Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice.
    Am J Pathol. 2000 Mar;156(3):951-64 PMID: 10702411
  104. A far-downstream hepatocyte-specific control region directs expression of the linked human apolipoprotein E and C-I genes in transgenic mice.
    J Biol Chem. 1993 Apr 15;268(11):8221-9 PMID: 7681840
  105. Two distal downstream enhancers direct expression of the human apolipoprotein E gene to astrocytes in the brain.
    J Neurosci. 2001 Feb 1;21(3):812-22 PMID: 11157067
  106. Isolation and characterization of apolipoproteins from murine microglia. Identification of a low density lipoprotein-like apolipoprotein J-rich but E-poor spherical particle.
    J Biol Chem. 2000 Oct 13;275(41):31770-7 PMID: 10918055
  107. Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation.
    J Neurosci. 2002 Dec 15;22(24):10539-48 PMID: 12486146
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.5476-05.2006
Published
2006-05-10
Pages
4985-94
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6674234
Subset
IM
Grants
NIA NIH HHS · P01 AG022074 · United States
NHLBI NIH HHS · R01 HL37063 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.5476-05.2006 PMC Full Text View journal details
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