Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store

Abstract

Summary Evidence accumulated over more than two decades has implicated Ca 2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca 2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging‐related increases in the slow afterhyperpolarization, Ca 2+ spikes and currents, Ca 2+ transients, and L‐type voltage‐gated Ca 2+ channel (L‐VGCC) activity. Several of these changes have been associated with age‐related deficits in learning or memory. Consequently, one version of the Ca 2+ hypothesis has been that increased L‐VGCC activity drives many of the other Ca 2+ ‐related biomarkers of hippocampal aging. In addition, other studies have reported aging‐ or AD model‐related alterations in Ca 2+ release from ryanodine receptors (RyR) on intracellular stores. The Ca 2+ ‐sensitive RyR channels amplify plasmalemmal Ca 2+ influx by the mechanism of Ca 2+ ‐induced Ca 2+ release (CICR). Considerable evidence indicates that a preferred functional link is present between L‐VGCCs and RyRs which operate in series in heart and some brain cells. Here, we review studies implicating RyRs in altered Ca 2+ regulation in cell toxicity, aging, and AD. A recent study from our laboratory showed that increased CICR plays a necessary role in the emergence of Ca 2+ ‐related biomarkers of aging. Consequently, we propose an expanded L‐VGCC/Ca 2+ hypothesis, in which aging/pathological changes occur in both L‐type Ca 2+ channels and RyRs, and interact to abnormally amplify Ca 2+ transients. In turn, the increased transients result in dysregulation of multiple Ca 2+ ‐dependent processes and, through somewhat different pathways, in accelerated functional decline during aging and AD.

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References 166

1. 1.

   Aley PK, Murray HJ, Boyle JP, Pearson HA, Peers C. Hypoxia stimulates Ca2+ release from intracellular stores in astrocytes via cyclic ADP ribose-mediated activation of ryanodine receptors. Cell Calcium. 2006;39:95-100.

   Not in our library10.1016/j.ceca.2005.09.009

2. 2.

   Alonso MT, Barrero MJ, Carnicero E, Montero M, Garcia-Sancho J, Alvarez J. Functional measurements of [Ca2+] in the endoplasmic reticulum using a herpes virus to deliver targeted aequorin. Cell Calcium. 1998;24:87-96.

   Not in our library10.1016/s0143-4160(98)90076-8

3. 3.

   Alonso MT, Barrero MJ, Michelena P, Carnicero E, Cuchillo I, Garcia AG, Garcia-Sancho J, Montero M, Alvarez J. Ca2+-induced Ca2+ release in chromaffin cells seen from inside the ER with targeted aequorin. J. Cell Biol. 1999;144:241-254.

   Not in our library10.1083/jcb.144.2.241

4. 4.

   Alshuaib WB, Cherian SP, Hasan MY, Fahim MA. Modulation of neuronal [Ca2+]i by caffeine is altered with aging. Int. J. Dev. Neurosci. 2006;24:389-394.

   Not in our library10.1016/j.ijdevneu.2006.05.006

5. 5.

   Ankarcrona M, Hultenby K. Presenilin-1 is located in rat mitochondria. Biochem. Biophys. Res. Commun. 2002;295:766-770.

   Not in our library10.1016/s0006-291x(02)00735-0

6. 6.

   Araki T, Kato H, Kanai Y, Kogure K. Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain. J. Neural Transm. Gen. Sect. 1994;97:135-147.

   Not in our library10.1007/bf01277949

7. 7.

   Attucci S, Clodfelter GV, Thibault O, Staton J, Moroni F, Landfield PW, Porter NM. Group I metabotropic glutamate receptor inhibition selectively blocks a prolonged Ca(2+) elevation associated with age-dependent excitotoxicity. Neuroscience. 2002;112:183-194.

   Not in our library10.1016/s0306-4522(02)00002-7

8. 8.

   Barnes CA. Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 1994;17:13-18.

   Not in our library10.1016/0166-2236(94)90029-9

9. 9.

   Barnes CA, Rao G, Shen J. Age-related decrease in the N-methyl-D-aspartateR-mediated excitatory postsynaptic potential in hippocampal region CA1. Neurobiol. Aging. 1997;18:445-452.

   Not in our library10.1016/s0197-4580(97)00044-4

10. 10.

    Begley JG, Duan W, Chan S, Duff K, Mattson MP. Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice. J. Neurochem. 1999;72:1030-1039.

    Not in our library10.1046/j.1471-4159.1999.0721030.x

11. 11.

    Behbahani H, Shabalina IG, Wiehager B, Concha H, Hultenby K, Petrovic N, Nedergaard J, Winblad B, Cowburn RF, Ankarcrona M. Differential role of Presenilin-1 and -2 on mitochondrial membrane potential and oxygen consumption in mouse embryonic fibroblasts. J. Neurosci. Res. 2006;84:891-902.

    Not in our library10.1002/jnr.20990

12. 12.

    Berridge MJ. Inositol trisphosphate and calcium signalling. Nature. 1993;361:315-325.

    Not in our library10.1038/361315a0

13. 13.

    Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium. 2002;32:235-249.

    Not in our library10.1016/s0143416002001823

14. 14.

    Bezprozvanny I, Watras J, Ehrlich BE. Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature. 1991;351:751-754.

    Not in our library10.1038/351751a0

15. 15.

    Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW. Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc. Natl Acad. Sci. USA. 2004;101:2173-2178.

    Not in our library10.1073/pnas.0308512100

16. 16.

    Bobich JA, Zheng Q, Campbell A. Incubation of nerve endings with a physiological concentration of Abeta1-42 activates CaV2.2(N-Type)-voltage operated calcium channels and acutely increases glutamate and noradrenaline release. J. Alzheimers Dis. 2004;6:243-255.

    Not in our library10.3233/jad-2004-6305

17. 17.

    Bootman MD, Collins TJ, Peppiatt CM, Prothero LS, MacKenzie L, De Smet P, Travers M, Tovey SC, Seo JT, Berridge MJ, Ciccolini F, Lipp P. Calcium signalling – an overview. Semin. Cell Dev. Biol. 2001;12:3-10.

    Not in our library10.1006/scdb.2000.0211

18. 18.

    Borde M, Bonansco C, de Sevilla F, Le Ray D, Buno W. Voltage-clamp analysis of the potentiation of the slow Ca2+-activated K+ current in hippocampal pyramidal neurons. Hippocampus. 2000;10:198-206.

    Not in our library10.1002/(sici)1098-1063(2000)10:2<198::aid-hipo9>3.0.co;2-f

19. 19.

    Brown TH, Jaffe DB. Calcium imaging in hippocampal neurons using confocal microscopy. Ann. N. Y. Acad. Sci. 1994;747:313-324.

    Not in our library10.1111/j.1749-6632.1994.tb44419.x

20. 20.

    Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat. Rev. Neurosci. 2006;7:30-40.

    Not in our library10.1038/nrn1809

21. 21.

    Campbell LW, Hao SY, Thibault O, Blalock EM, Landfield PW. Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons. J. Neurosci. 1996;16:6286-6295.

    Not in our library10.1523/jneurosci.16-19-06286.1996

22. 22.

    Carafoli E. Calcium signaling: a tale for all seasons. Proc. Natl Acad. Sci. USA. 2002;99:1115-1122.

    Not in our library10.1073/pnas.032427999

23. 23.

    Chan SL, Culmsee C, Haughey N, Klapper W, Mattson MP. Presenilin-1 mutations sensitize neurons to DNA damage-induced death by a mechanism involving perturbed calcium homeostasis and activation of calpains and caspase-12. Neurobiol. Dis. 2002;11:2-19.

    Not in our library10.1006/nbdi.2002.0542

24. 24.

    Chan SL, Mayne M, Holden CP, Geiger JD, Mattson MP. Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons. J. Biol. Chem. 2000;275:18195-18200.

    Not in our library10.1074/jbc.m000040200

25. 25.

    Chavis P, Fagni L, Lansman JB, Bockaert J. Functional coupling between ryanodine receptors and L-type calcium channels in neurons. Nature. 1996;382:719-722.

    Not in our library10.1038/382719a0

26. 26.

    Cheng G, Liu BF, Yu Y, Diglio C, Kuo TH. The exit from G(0) into the cell cycle requires and is controlled by sarco(endo)plasmic reticulum Ca2+ pump. Arch. Biochem. Biophys. 1996;329:65-72.

    Not in our library10.1006/abbi.1996.0192

27. 27.

    Choi DW. Excitotoxic cell death. J. Neurobiol. 1992;23:1261-1276.

    Not in our library10.1002/neu.480230915

28. 28.

    Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J. Neurosci. 1987;7:357-368.

    Not in our library10.1523/jneurosci.07-02-00357.1987

29. 29.

    Clodfelter GV, Porter NM, Landfield PW, Thibault O. Sustained Ca2+-induced Ca2+-release underlies the post-glutamate lethal Ca2+ plateau in older cultured hippocampal neurons. Eur. J. Pharmacol. 2002;447:189-200.

    Not in our library10.1016/s0014-2999(02)01843-5

30. 30.

    Cook DG, Li X, Cherry SD, Cantrell AR. Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons. J. Neurophysiol. 2005;94:4421-4429.

    Not in our library10.1152/jn.00745.2005

31. 31.

    Coronado R, Morrissette J, Sukhareva M, Vaughan DM. Structure and function of ryanodine receptors. Am. J. Physiol. 1994;266:C1485-C1504.

    Not in our library10.1152/ajpcell.1994.266.6.c1485

32. 32.

    Davidson RM, Shajenko L, Donta TS. Amyloid β-peptide (A β P) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastoma cells. Brain Res. 1994;643:324-327.

    Not in our library10.1016/0006-8993(94)90041-8

33. 33.

    Dawson AP. Calcium signalling: how do IP3 receptors work? Curr. Biol. 1997;7:R544-R547.

    Not in our library10.1016/s0960-9822(06)00277-6

34. 34.

    Deyo RA, Straube KT, Disterhoft JF. Nimodipine facilitates associative learning in aging rabbits. Science. 1989;243:809-811.

    Not in our library10.1126/science.2916127

35. 35.

    Disterhoft JF, Moyer JR, Thompson LT. The calcium rationale in aging and Alzheimer's disease. Evidence from an animal model of normal aging. Ann. N. Y. Acad. Sci. 1994;747:382-406.

    Not in our library10.1111/j.1749-6632.1994.tb44424.x

36. 36.

    Disterhoft JF, Thompson LT, Moyer JR, Mogul DJ. Calcium-dependent afterhyperpolarization and learning in young and aging hippocampus. Life Sci. 1996;59:413-420.

    Not in our library10.1016/0024-3205(96)00320-7

37. 37.

    Disterhoft JF, Wu WW, Ohno M. Biophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer's disease. Ageing Res. Rev. 2004;3:383-406.

    Not in our library10.1016/j.arr.2004.07.001

38. 38.

    Doutheil J, Treiman M, Oschlies U, Paschen W. Recovery of neuronal protein synthesis after irreversible inhibition of the endoplasmic reticulum calcium pump. Cell Calcium. 1999;25:419-428.

    Not in our library10.1054/ceca.1999.0042

39. 39.

    Dubinsky JM. Intracellular calcium levels during the period of delayed excitotoxicity. J. Neurosci. 1993;13:623-631.

    Not in our library10.1523/jneurosci.13-02-00623.1993

40. 40.

    Duffy S, MacVicar BA. In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes. J. Neurosci. 1996;16:71-81.

    Not in our library10.1523/jneurosci.16-01-00071.1996

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