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Open Access 01-12-2009 | Research article

ApoE isoform-dependent changes in hippocampal synaptic function

Authors: Kimberly M Korwek, Justin H Trotter, Mary Jo LaDu, Patrick M Sullivan, Edwin J Weeber

Published in: Molecular Neurodegeneration | Issue 1/2009

Abstract

The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR) mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP) is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.

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Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993, 261: 921-923. 10.1126/science.8346443.CrossRefPubMed

Rebeck GW, Reiter JS, Strickland DK, Hyman BT: Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron. 1993, 11: 575-580. 10.1016/0896-6273(93)90070-8.CrossRefPubMed

Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD: 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 USA. 1993, 90: 1977-1981. 10.1073/pnas.90.5.1977.PubMedCentralCrossRefPubMed

Beffert U, Stolt PC, Herz J: Functions of lipoprotein receptors in neurons. J Lipid Res. 2004, 45: 403-409. 10.1194/jlr.R300017-JLR200.CrossRefPubMed

Qiu S, Korwek KM, Weeber EJ: A fresh look at an ancient receptor family: emerging roles for low density lipoprotein receptors in synaptic plasticity and memory formation. Neurobiol Learn Mem. 2006, 85: 16-29. 10.1016/j.nlm.2005.08.009.CrossRefPubMed

Koch S, Strasser V, Hauser C, Fasching D, Brandes C, Bajari TM, Schneider WJ, Nimpf J: A secreted soluble form of ApoE receptor 2 acts as a dominant-negative receptor and inhibits Reelin signaling. Embo J. 2002, 21: 5996-6004. 10.1093/emboj/cdf599.PubMedCentralCrossRefPubMed

Nakajima K, Mikoshiba K, Miyata T, Kudo C, Ogawa M: Disruption of hippocampal development in vivo by CR-50 mAb against reelin. Proc Natl Acad Sci USA. 1997, 94: 8196-8201. 10.1073/pnas.94.15.8196.PubMedCentralCrossRefPubMed

Qiu S, Korwek KM, Pratt-Davis AR, Peters M, Bergman MY, Weeber EJ: Cognitive disruption and altered hippocampus synaptic function in Reelin haploinsufficient mice. Neurobiol Learn Mem. 2006, 85: 228-242. 10.1016/j.nlm.2005.11.001.CrossRefPubMed

Weeber EJ, Beffert U, Jones C, Christian JM, Forster E, Sweatt JD, Herz J: Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J Biol Chem. 2002, 277: 39944-39952. 10.1074/jbc.M205147200.CrossRefPubMed

10.

Trommsdorff M, Gotthardt M, Hiesberger T, Shelton J, Stockinger W, Nimpf J, Hammer RE, Richardson JA, Herz J: Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell. 1999, 97: 689-701. 10.1016/S0092-8674(00)80782-5.CrossRefPubMed

11.

Sullivan PM, Mezdour H, Aratani Y, Knouff C, Najib J, Reddick RL, Quarfordt SH, Maeda N: Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem. 1997, 272: 17972-17980. 10.1074/jbc.272.29.17972.CrossRefPubMed

12.

Kim DH, Iijima H, Goto K, Sakai J, Ishii H, Kim HJ, Suzuki H, Kondo H, Saeki S, Yamamoto T: Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J Biol Chem. 1996, 271: 8373-8380. 10.1074/jbc.271.14.8373.CrossRefPubMed

13.

Nimpf J, Schneider WJ: The VLDL receptor: an LDL receptor relative with eight ligand binding repeats, LR8. Atherosclerosis. 1998, 141: 191-202. 10.1016/S0021-9150(98)00172-5.CrossRefPubMed

14.

Grootendorst J, Bour A, Vogel E, Kelche C, Sullivan PM, Dodart JC, Bales K, Mathis C: Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. Behav Brain Res. 2005, 159: 1-14. 10.1016/j.bbr.2004.09.019.CrossRefPubMed

15.

Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Ye GL, Sotak M, Sullivan PM, Pasternak JF, LaDu MJ: ApoE isoform affects LTP in human targeted replacement mice. Neuroreport. 2004, 15: 2655-2658. 10.1097/00001756-200412030-00020.CrossRefPubMed

16.

Kitamura HW, Hamanaka H, Watanabe M, Wada K, Yamazaki C, Fujita SC, Manabe T, Nukina N: Age-dependent enhancement of hippocampal long-term potentiation in knock-in mice expressing human apolipoprotein E4 instead of mouse apolipoprotein E. Neurosci Lett. 2004, 369: 173-178. 10.1016/j.neulet.2004.07.084.CrossRefPubMed

17.

Larson J, Wong D, Lynch G: Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res. 1986, 368: 347-350. 10.1016/0006-8993(86)90579-2.CrossRefPubMed

18.

Larson J, Lynch G: Role of N-methyl-D-aspartate receptors in the induction of synaptic potentiation by burst stimulation patterned after the hippocampal theta-rhythm. Brain Res. 1988, 441: 111-118. 10.1016/0006-8993(88)91388-1.CrossRefPubMed

19.

Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Blaine Stine W, Manelli A, Sullivan P, Pasternak JF, LaDu MJ: ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. Neurobiol Dis. 2005, 18: 75-82. 10.1016/j.nbd.2004.08.011.CrossRefPubMed

20.

Abraham WC, Huggett A: Induction and reversal of long-term potentiation by repeated high-frequency stimulation in rat hippocampal slices. Hippocampus. 1997, 7: 137-145. 10.1002/(SICI)1098-1063(1997)7:2<137::AID-HIPO3>3.0.CO;2-K.CrossRefPubMed

21.

Qiu S, Weeber EJ: Reelin signaling facilitates maturation of CA1 glutamatergic synapses. J Neurophysiol. 2007, 97: 2312-2321. 10.1152/jn.00869.2006.CrossRefPubMed

22.

Sinagra M, Verrier D, Frankova D, Korwek KM, Blahos J, Weeber EJ, Manzoni OJ, Chavis P: Reelin, very-low-density lipoprotein receptor, and apolipoprotein E receptor 2 control somatic NMDA receptor composition during hippocampal maturation in vitro. J Neurosci. 2005, 25: 6127-6136. 10.1523/JNEUROSCI.1757-05.2005.CrossRefPubMed

23.

Qiu S, Zhao LF, Korwek KM, Weeber EJ: Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus. J Neurosci. 2006, 26: 12943-12955. 10.1523/JNEUROSCI.2561-06.2006.CrossRefPubMed

24.

Rebeck GW, Ladu MJ, Estus S, Bu G, Weeber EJ: The generation and function of soluble apoE receptors in the CNS. Mol Neurodegener. 2006, 1: 15-10.1186/1750-1326-1-15.PubMedCentralCrossRefPubMed

25.

Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, Li WP, Adelmann G, Frotscher M, Hammer RE, Herz J: Modulation of synaptic plasticity and memory by reelin involves differential splicing of the lipoprotein receptor apoER2. Neuron. 2005, 47: 567-579. 10.1016/j.neuron.2005.07.007.CrossRefPubMed

26.

Riddell DR, Zhou H, Atchison K, Warwick HK, Atkinson PJ, Jefferson J, Xu L, Aschmies S, Kirksey Y, Hu Y, et al: Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J Neurosci. 2008, 28: 11445-11453. 10.1523/JNEUROSCI.1972-08.2008.CrossRefPubMed

27.

Ferrani-Kile K, Leslie SW: Modulation of protein tyrosine phosphatase activity alters the subunit assembly in native N-methyl-D-aspartate receptor complex. J Pharmacol Exp Ther. 2005, 314: 86-93. 10.1124/jpet.105.083535.CrossRefPubMed

28.

Goebel SM, Alvestad RM, Coultrap SJ, Browning MD: Tyrosine phosphorylation of the N-methyl-D-aspartate receptor is enhanced in synaptic membrane fractions of the adult rat hippocampus. Brain Res Mol Brain Res. 2005, 142: 65-79.CrossRefPubMed

29.

Lu YM, Roder JC, Davidow J, Salter MW: Src activation in the induction of long-term potentiation in CA1 hippocampal neurons. Science. 1998, 279: 1363-1367. 10.1126/science.279.5355.1363.CrossRefPubMed

30.

Tezuka T, Umemori H, Akiyama T, Nakanishi S, Yamamoto T: PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. Proc Natl Acad Sci USA. 1999, 96: 435-440. 10.1073/pnas.96.2.435.PubMedCentralCrossRefPubMed

31.

Hoe HS, Harris DC, Rebeck GW: Multiple pathways of apolipoprotein E signaling in primary neurons. J Neurochem. 2005, 93: 145-155. 10.1111/j.1471-4159.2004.03007.x.CrossRefPubMed

32.

Bock HH, Herz J: Reelin activates SRC family tyrosine kinases in neurons. Curr Biol. 2003, 13: 18-26. 10.1016/S0960-9822(02)01403-3.CrossRefPubMed

33.

Chen Y, Beffert U, Ertunc M, Tang TS, Kavalali ET, Bezprozvanny I, Herz J: Reelin modulates NMDA receptor activity in cortical neurons. J Neurosci. 2005, 25: 8209-8216. 10.1523/JNEUROSCI.1951-05.2005.CrossRefPubMed

34.

Groc L, Choquet D, Stephenson FA, Verrier D, Manzoni OJ, Chavis P: NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein Reelin. J Neurosci. 2007, 27: 10165-10175. 10.1523/JNEUROSCI.1772-07.2007.CrossRefPubMed

35.

Hugues S, Chessel A, Lena I, Marsault R, Garcia R: Prefrontal infusion of PD098059 immediately after fear extinction training blocks extinction-associated prefrontal synaptic plasticity and decreases prefrontal ERK2 phosphorylation. Synapse. 2006, 60: 280-287. 10.1002/syn.20291.CrossRefPubMed

36.

Zhang JJ, Okutani F, Inoue S, Kaba H: Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway leading to cyclic AMP response element-binding protein phosphorylation is required for the long-term facilitation process of aversive olfactory learning in young rats. Neuroscience. 2003, 121: 9-16. 10.1016/S0306-4522(03)00392-0.CrossRefPubMed

37.

Cestari V, Costanzi M, Castellano C, Rossi-Arnaud C: A role for ERK2 in reconsolidation of fear memories in mice. Neurobiol Learn Mem. 2006, 86: 133-143. 10.1016/j.nlm.2006.01.003.CrossRefPubMed

38.

Fischer A, Radulovic M, Schrick C, Sananbenesi F, Godovac-Zimmermann J, Radulovic J: Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior. Neurobiol Learn Mem. 2007, 87: 149-158. 10.1016/j.nlm.2006.08.003.PubMedCentralCrossRefPubMed

39.

Giovannini MG: The role of the extracellular signal-regulated kinase pathway in memory encoding. Rev Neurosci. 2006, 17: 619-634.PubMed

40.

Olson GE, Winfrey VP, Nagdas SK, Hill KE, Burk RF: Apolipoprotein E receptor-2 (apoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J Biol Chem. 2007, 282: 12290-12297. 10.1074/jbc.M611403200.CrossRefPubMed

Title: ApoE isoform-dependent changes in hippocampal synaptic function
Authors: Kimberly M Korwek
Justin H Trotter
Mary Jo LaDu
Patrick M Sullivan
Edwin J Weeber
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2009
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-4-21

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ApoE isoform-dependent changes in hippocampal synaptic function

Abstract

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Abstract

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