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Molecular Neurobiology

, Volume 56, Issue 12, pp 8035–8051 | Cite as

Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment

  • C. Toledo
  • D. C. Andrade
  • H. S. Díaz
  • N. C. Inestrosa
  • R. Del RioEmail author
Article
  • 348 Downloads

Abstract

Heart failure (HF) is a major public health issue affecting more than 26 million people worldwide. HF is the most common cardiovascular disease in elder population; and it is associated with neurocognitive function decline, which represent underlying brain pathology diminishing learning and memory faculties. Both HF and neurocognitive impairment are associated with recurrent hospitalization episodes and increased mortality rate in older people, but particularly when they occur simultaneously. Overall, the published studies seem to confirm that HF patients display functional impairments relating to attention, memory, concentration, learning, and executive functioning compared with age-matched controls. However, little is known about the molecular mechanisms underpinning neurocognitive decline in HF. The present review round step recent evidence related to the possible molecular mechanism involved in the establishment of neurocognitive disorders during HF. We will make a special focus on cerebral ischemia, neuroinflammation and oxidative stress, Wnt signaling, and mitochondrial DNA alterations as possible mechanisms associated with cognitive decline in HF. Also, we provide an integrative mechanism linking pathophysiological hallmarks of altered cardiorespiratory control and the development of cognitive dysfunction in HF patients.

Graphical Abstract

Main molecular mechanisms involved in the establishment of cognitive impairment during heart failure. Heart failure is characterized by chronic activation of brain areas responsible for increasing cardiac sympathetic load. In addition, HF patients also show neurocognitive impairment, suggesting that the overall mechanisms that underpin cardiac sympathoexcitation may be related to the development of cognitive disorders in HF. In low cardiac output, HF cerebral infarction due to cardiac mural emboli and cerebral ischemia due to chronic or intermittent cerebral hypoperfusion has been described as a major mechanism related to the development of CI. In addition, while acute norepinephrine (NE) release may be relevant to induce neural plasticity in the hippocampus, chronic or tonic release of NE may exert the opposite effects due to desensitization of the adrenergic signaling pathway due to receptor internalization. Enhanced chemoreflex drive is a major source of sympathoexcitation in HF, and this phenomenon elevates brain ROS levels and induces neuroinflammation through breathing instability. Importantly, both oxidative stress and neuroinflammation can induce mitochondrial dysfunction and vice versa. Then, this ROS inflammatory pathway may propagate within the brain and potentially contribute to the development of cognitive impairment in HF through the activation/inhibition of key molecular pathways involved in neurocognitive decline such as the Wnt signaling pathway.

Keywords

Heart failure Cognitive impairment Aging Cardiorespiratory control Signal pathway 

Notes

Acknowledgments

Figures were designed with elements provided by Servier Medical Art (https://smart.servier.com).

Funding Information

This work was supported by the Fondo de Desarrollo Científico y Tecnológico (Fondecyt) (grant number 1180172), the Basal Center of Excellence in Aging and Regeneration (AFB 170005), and the special grant “Lithium in Health and Disease” from the Sociedad Química y Minera de Chile (SQM).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, Nodari S, Lam CSP et al (2014) The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol 63(12):1123–1133.  https://doi.org/10.1016/j.jacc.2013.11.053
  2. 2.
    Ponikowski P, Anker SD, AlHabib KF, Cowie MR, Force TL, Hu S, Jaarsma T, Krum H et al (2014) Heart failure: preventing disease and death worldwide. ESC Heart Fail 1(1):4–25.  https://doi.org/10.1002/ehf2.12005
  3. 3.
    Mosterd A, Hoes AW (2007) Clinical epidemiology of heart failure. Heart 93(9):1137–1146.  https://doi.org/10.1136/hrt.2003.025270 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S et al (2016) Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133(4):e38–e360.  https://doi.org/10.1161/CIR.0000000000000350
  5. 5.
    Savarese G, Lund LH (2017) Global public health burden of heart failure. Cardiac Fail Rev 3(1):7–11.  https://doi.org/10.15420/cfr.2016:25:2 CrossRefGoogle Scholar
  6. 6.
    Go YY, Allen JC, Chia SY, Sim LL, Jaufeerally FR, Yap J, Ching CK, Sim D et al (2014) Predictors of mortality in acute heart failure: interaction between diabetes and impaired left ventricular ejection fraction. Eur J Heart Fail 16(11):1183–1189.  https://doi.org/10.1002/ejhf.119
  7. 7.
    Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, Ikonomidis JS, Khavjou O et al (2013) Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail 6(3):606–619.  https://doi.org/10.1161/HHF.0b013e318291329a
  8. 8.
    Leto L, Feola M (2014) Cognitive impairment in heart failure patients. J Geriatr Cardiol 11(4):316–328.  https://doi.org/10.11909/j.issn.1671-5411.2014.04.007 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Alagiakrishnan K, Mah D, Dyck JR, Senthilselvan A, Ezekowitz J (2017) Comparison of two commonly used clinical cognitive screening tests to diagnose mild cognitive impairment in heart failure with the golden standard European Consortium Criteria. Int J Cardiol 228:558–562.  https://doi.org/10.1016/j.ijcard.2016.11.193 CrossRefPubMedGoogle Scholar
  10. 10.
    Cameron J, Gallagher R, Pressler SJ (2017) Detecting and managing cognitive impairment to improve engagement in heart failure self-care. Curr Heart Fail Rep 14(1):13–22.  https://doi.org/10.1007/s11897-017-0317-0 CrossRefPubMedGoogle Scholar
  11. 11.
    Leto L, Feola M (2015) Cognitive impairment in heart failure patients: role of atrial fibrillation. J Geriatr Cardiol 12(6):690.  https://doi.org/10.11909/j.issn.1671-5411.2015.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Qiu C, Winblad B, Marengoni A, Klarin I, Fastbom J, Fratiglioni L (2006) Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study. Arch Intern Med 166(9):1003–1008.  https://doi.org/10.1001/archinte.166.9.1003 CrossRefPubMedGoogle Scholar
  13. 13.
    Tilvis RS, Kahonen-Vare MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE (2004) Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 59(3):268–274CrossRefGoogle Scholar
  14. 14.
    Vogels RL, Scheltens P, Schroeder-Tanka JM, Weinstein HC (2007) Cognitive impairment in heart failure: a systematic review of the literature. Eur J Heart Fail 9(5):440–449.  https://doi.org/10.1016/j.ejheart.2006.11.001 CrossRefPubMedGoogle Scholar
  15. 15.
    Mayou R, Blackwood R, Bryant B, Garnham J (1991) Cardiac failure: symptoms and functional status. J Psychosom Res 35(4-5):399–407CrossRefGoogle Scholar
  16. 16.
    Dickson VV, Tkacs N, Riegel B (2007) Cognitive influences on self-care decision making in persons with heart failure. Am Heart J 154(3):424–431.  https://doi.org/10.1016/j.ahj.2007.04.058 CrossRefPubMedGoogle Scholar
  17. 17.
    Wu JR, Moser DK, Lennie TA, Peden AR, Chen YC, Heo S (2008) Factors influencing medication adherence in patients with heart failure. Heart Lung 37(1):8–16, 16.e11.  https://doi.org/10.1016/j.hrtlng.2007.02.003 CrossRefPubMedGoogle Scholar
  18. 18.
    Murad K, Goff DC Jr, Morgan TM, Burke GL, Bartz TM, Kizer JR, Chaudhry SI, Gottdiener JS et al (2015) Burden of comorbidities and functional and cognitive impairments in elderly patients at the initial diagnosis of heart failure and their impact on total mortality. Cardiovasc Health Study JACC Heart Fail 3(7):542–550.  https://doi.org/10.1016/j.jchf.2015.03.004
  19. 19.
    Heckman GA, Patterson CJ, Demers C, St Onge J, Turpie ID, McKelvie RS (2007) Heart failure and cognitive impairment: challenges and opportunities. Clin Interv Aging 2(2):209–218PubMedPubMedCentralGoogle Scholar
  20. 20.
    Oliveira BF, Nogueira-Machado JA, Chaves MM (2010) The role of oxidative stress in the aging process. TheScientificWorldJOURNAL 10:1121–1128.  https://doi.org/10.1100/tsw.2010.94 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wei YH, Lee HC (2002) Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood, NJ) 227(9):671–682CrossRefGoogle Scholar
  22. 22.
    Duan MJ, Yan ML, Wang Q, Mao M, Su D, Sun LL, Li KX, Qu Y et al (2018) Overexpression of miR-1 in the heart attenuates hippocampal synaptic vesicle exocytosis by the posttranscriptional regulation of SNAP-25 through the transportation of exosomes. Cell Commun Signal 16(1):91.  https://doi.org/10.1186/s12964-018-0303-5
  23. 23.
    Li A, Zhou C, Moore J, Zhang P, Tsai TH, Lee HC, Romano DM, McKee ML et al (2011) Changes in the expression of the Alzheimer’s disease-associated presenilin gene in drosophila heart leads to cardiac dysfunction. Curr Alzheimer Res 8(3):313–322Google Scholar
  24. 24.
    Yancy Clyde W, Jessup M, Bozkurt B, Butler J, Casey Donald E, Colvin Monica M, Drazner Mark H, Filippatos Gerasimos S et al (2017) 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Failure Society of America. Circulation 136(6):e137–e161.  https://doi.org/10.1161/CIR.0000000000000509
  25. 25.
    Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 35(3):569–582CrossRefGoogle Scholar
  26. 26.
    Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ et al (2008) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 10(10):933–989.  https://doi.org/10.1016/j.ejheart.2008.08.005
  27. 27.
    Oktay AA, Rich JD, Shah SJ (2013) The emerging epidemic of heart failure with preserved ejection fraction. Curre Heart Fail Rep 10(4):401–410.  https://doi.org/10.1007/s11897-013-0155-7 CrossRefGoogle Scholar
  28. 28.
    Aguero-Torres H, Thomas VS, Winblad B, Fratiglioni L (2002) The impact of somatic and cognitive disorders on the functional status of the elderly. J Clin Epidemiol 55(10):1007–1012CrossRefGoogle Scholar
  29. 29.
    Murman DL (2015) The impact of age on cognition. Semin Hear 36(03):111–121.  https://doi.org/10.1055/s-0035-1555115 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Cacciatore F, Abete P, Ferrara N, Calabrese C, Napoli C, Maggi S, Varricchio M, Rengo F (1998) Congestive heart failure and cognitive impairment in an older population. Osservatorio Geriatrico Campano Study Group. J Am Geriatr Soc 46(11):1343–1348CrossRefGoogle Scholar
  31. 31.
    Frey A, Sell R, Homola GA, Malsch C, Kraft P, Gunreben I, Morbach C, Alkonyi B et al (2018) Cognitive deficits and related brain lesions in patients with chronic heart failure. JACC Heart Fail 6(7):583–592.  https://doi.org/10.1016/j.jchf.2018.03.010
  32. 32.
    Borson S (2010) Cognition, aging, and disabilities: conceptual issues. Phys Med Rehabil Clin N Am 21(2):375–382.  https://doi.org/10.1016/j.pmr.2010.01.001 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Levin SN, Hajduk AM, McManus DD, Darling CE, Gurwitz JH, Spencer FA, Goldberg RJ, Saczynski JS (2014) Cognitive status in patients hospitalized with acute decompensated heart failure. Am Heart J 168(6):917–923.  https://doi.org/10.1016/j.ahj.2014.08.008 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Cline CM, Bjorck-Linne AK, Israelsson BY, Willenheimer RB, Erhardt LR (1999) Non-compliance and knowledge of prescribed medication in elderly patients with heart failure. Eur J Heart Fail 1(2):145–149CrossRefGoogle Scholar
  35. 35.
    Harkness K, Demers C, Heckman GA, McKelvie RS (2011) Screening for cognitive deficits using the Montreal cognitive assessment tool in outpatients >/=65 years of age with heart failure. Am J Cardiol 107(8):1203–1207.  https://doi.org/10.1016/j.amjcard.2010.12.021 CrossRefPubMedGoogle Scholar
  36. 36.
    Bennett SJ, Sauve MJ, Shaw RM (2005) A conceptual model of cognitive deficits in chronic heart failure. J Nurs Scholarsh 37(3):222–228CrossRefGoogle Scholar
  37. 37.
    Premen AJ, Panel fNCAA (1996) Research recommendations for cardiovascular aging research. J Am Geriatr Soc 44(9):1114–1117.  https://doi.org/10.1111/j.1532-5415.1996.tb02950.x CrossRefPubMedGoogle Scholar
  38. 38.
    Zuccala G, Cattel C, Manes-Gravina E, Di Niro MG, Cocchi A, Bernabei R (1997) Left ventricular dysfunction: a clue to cognitive impairment in older patients with heart failure. J Neurol Neurosurg Psychiatry 63(4):509–512CrossRefGoogle Scholar
  39. 39.
    Dodson JA, Truong TT, Towle VR, Kerins G, Chaudhry SI (2013) Cognitive impairment in older adults with heart failure: prevalence, documentation, and impact on outcomes. Am J Med 126(2):120–126.  https://doi.org/10.1016/j.amjmed.2012.05.029 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Cannon JA, Moffitt P, Perez-Moreno AC, Walters MR, Broomfield NM, McMurray JJV, Quinn TJ (2017) Cognitive impairment and heart failure: systematic review and meta-analysis. J Card Fail 23(6):464–475.  https://doi.org/10.1016/j.cardfail.2017.04.007 CrossRefPubMedGoogle Scholar
  41. 41.
    Pressler SJ, Kim J, Riley P, Ronis DL, Gradus-Pizlo I (2010) Memory dysfunction, psychomotor slowing, and decreased executive function predict mortality in patients with heart failure and low ejection fraction. J Card Fail 16(9):750–760.  https://doi.org/10.1016/j.cardfail.2010.04.007 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Miller LA, Spitznagel MB, Alosco ML, Cohen RA, Raz N, Sweet LH, Colbert L, Josephson R et al (2012) Cognitive profiles in heart failure: a cluster analytic approach. J Clin Exp Neuropsychol 34(5):509–520.  https://doi.org/10.1080/13803395.2012.663344
  43. 43.
    Bratzke-Bauer LC, Pozehl BJ, Paul SM, Johnson JK (2013) Neuropsychological patterns differ by type of left ventricle dysfunction in heart failure. Arch Clin Neuropsychol 28(2):114–124.  https://doi.org/10.1093/arclin/acs101 CrossRefPubMedGoogle Scholar
  44. 44.
    Athilingam P, D’Aoust RF, Miller L, Chen L (2013) Cognitive profile in persons with systolic and diastolic heart failure. Congest Heart Fail (Greenwich, Conn) 19(1):44–50.  https://doi.org/10.1111/chf.12001 CrossRefGoogle Scholar
  45. 45.
    Hammond CA, Blades NJ, Chaudhry SI, Dodson JA, Longstreth WT Jr, Heckbert SR, Psaty BM, Arnold AM et al (2018) Long-term cognitive decline after newly diagnosed heart failure: longitudinal analysis in the chs (Cardiovascular Health Study). Circ Heart Fail 11(3):e004476.  https://doi.org/10.1161/circheartfailure.117.004476
  46. 46.
    Hajduk AM, Kiefe CI, Person SD, Gore JG, Saczynski JS (2013) Cognitive change in heart failure: a systematic review. Circ Cardiovasc Qual Outcomes 6(4):451–460.  https://doi.org/10.1161/circoutcomes.113.000121 CrossRefPubMedGoogle Scholar
  47. 47.
    Hong X, Bu L, Wang Y, Xu J, Wu J, Huang Y, Liu J, Suo H et al (2013) Increases in the risk of cognitive impairment and alterations of cerebral beta-amyloid metabolism in mouse model of heart failure. PLoS One 8(5):e63829.  https://doi.org/10.1371/journal.pone.0063829
  48. 48.
    Glisky EL (2007) Frontiers in Neuroscience Changes in Cognitive Function in Human Aging. In: Riddle DR (ed) Brain Aging: Models, Methods, and Mechanisms. CRC Press/Taylor & Francis Taylor & Francis Group, LLC., Boca Raton (FL)Google Scholar
  49. 49.
    Almeida OP, Garrido GJ, Beer C, Lautenschlager NT, Arnolda L, Flicker L (2012) Cognitive and brain changes associated with ischaemic heart disease and heart failure. Eur Heart J 33(14):1769–1776.  https://doi.org/10.1093/eurheartj/ehr467 CrossRefPubMedGoogle Scholar
  50. 50.
    Almeida OP, Garrido GJ, Etherton-Beer C, Lautenschlager NT, Arnolda L, Alfonso H, Flicker L (2013) Brain and mood changes over 2 years in healthy controls and adults with heart failure and ischaemic heart disease. Eur J Heart Fail 15(8):850–858.  https://doi.org/10.1093/eurjhf/hft029 CrossRefPubMedGoogle Scholar
  51. 51.
    Gaviria M, Pliskin N, Kney A (2011) Cognitive impairment in patients with advanced heart failure and its implications on decision-making capacity. Congest Heart Fail (Greenwich, Conn) 17(4):175–179.  https://doi.org/10.1111/j.1751-7133.2011.00242.x CrossRefGoogle Scholar
  52. 52.
    Riegel B, Lee CS, Dickson VV, Carlson B (2009) An update on the self-care of heart failure index. J Cardiovasc Nurs 24(6):485–497.  https://doi.org/10.1097/JCN.0b013e3181b4baa0 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Cameron J, Ski CF, McLennan SN, Rendell PG, Whitbourn RJ, Thompson DR (2014) Development of the Heart Failure Screening Tool (Heart-FaST) to measure barriers that impede engagement in self-care. Eur J Cardiovasc Nurs 13(5):408–417.  https://doi.org/10.1177/1474515113502461 CrossRefPubMedGoogle Scholar
  54. 54.
    Chaudhry SI, Wang Y, Gill TM, Krumholz HM (2010) Geriatric conditions and subsequent mortality in older patients with heart failure. J Am Coll Cardiol 55(4):309–316.  https://doi.org/10.1016/j.jacc.2009.07.066 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Sauve MJ, Lewis WR, Blankenbiller M, Rickabaugh B, Pressler SJ (2009) Cognitive impairments in chronic heart failure: a case controlled study. J Card Fail 15(1):1–10.  https://doi.org/10.1016/j.cardfail.2008.08.007 CrossRefPubMedGoogle Scholar
  56. 56.
    Rozzini R, Sabatini T, Trabucchi M (2004) Cognitive impairment and mortality in elderly patients with heart failure. Am J Med 116(2):137–138.  https://doi.org/10.1016/j.amjmed.2003.08.028 CrossRefPubMedGoogle Scholar
  57. 57.
    Zuccala G, Pedone C, Cesari M, Onder G, Pahor M, Marzetti E, Lo Monaco MR, Cocchi A et al (2003) The effects of cognitive impairment on mortality among hospitalized patients with heart failure. Am J Med 115(2):97–103Google Scholar
  58. 58.
    Bauer LC, Johnson JK, Pozehl BJ (2011) Cognition in heart failure: an overview of the concepts and their measures. J Am Acad Nurse Pract 23(11):577–585.  https://doi.org/10.1111/j.1745-7599.2011.00668.x CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Lepic T, Loncar G, Bozic B, Veljancic D, Labovic B, Krsmanovic Z, Lepic M, Raicevic R (2012) Cerebral blood flow in the chronic heart failure patients. Perspect Med 1(1):304–308.  https://doi.org/10.1016/j.permed.2012.02.057 CrossRefGoogle Scholar
  60. 60.
    Roman GC (2004) Brain hypoperfusion: a critical factor in vascular dementia. Neurol Res 26(5):454–458.  https://doi.org/10.1179/016164104225017686 CrossRefPubMedGoogle Scholar
  61. 61.
    Gruhn N, Larsen FS, Boesgaard S, Knudsen GM, Mortensen SA, Thomsen G, Aldershvile J (2001) Cerebral blood flow in patients with chronic heart failure before and after heart transplantation. Stroke 32(11):2530–2533CrossRefGoogle Scholar
  62. 62.
    Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80(4):844–866.  https://doi.org/10.1016/j.neuron.2013.10.008 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Zuccala G, Onder G, Pedone C, Carosella L, Pahor M, Bernabei R, Cocchi A (2001) Hypotension and cognitive impairment: selective association in patients with heart failure. Neurology 57(11):1986–1992CrossRefGoogle Scholar
  64. 64.
    Pullicino PM, Hart J (2001) Cognitive impairment in congestive heart failure?: embolism vs hypoperfusion. Neurology 57(11):1945–1946CrossRefGoogle Scholar
  65. 65.
    Gottesman RF, Grega MA, Bailey MM, Zeger SL, Baumgartner WA, McKhann GM, Selnes OA (2010) Association between hypotension, low ejection fraction and cognitive performance in cardiac patients. Behav Neurol 22(1-2):63–71.  https://doi.org/10.3233/ben-2009-0261 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Celutkiene J, Vaitkevicius A, Jakstiene S, Jatuzis D (2016) Expert opinion-cognitive decline in heart failure: more attention is needed. Cardiac Fail Rev 2(2):106–109.  https://doi.org/10.15420/cfr.2016:19:2 CrossRefGoogle Scholar
  67. 67.
    Bangen KJ, Nation DA, Clark LR, Harmell AL, Wierenga CE, Dev SI, Delano-Wood L, Zlatar ZZ et al (2014) Interactive effects of vascular risk burden and advanced age on cerebral blood flow. Front Aging Neurosci 6:159.  https://doi.org/10.3389/fnagi.2014.00159
  68. 68.
    Alosco ML, Spitznagel MB, Raz N, Cohen R, Sweet LH, Garcia S, Josephson R, van Dulmen M et al (2013) The interactive effects of cerebral perfusion and depression on cognitive function in older adults with heart failure. Psychosom Med 75(7):632–639.  https://doi.org/10.1097/PSY.0b013e31829f91da
  69. 69.
    Madhavan M, Graff-Radford J, Piccini JP, Gersh BJ (2018) Cognitive dysfunction in atrial fibrillation. Nat Rev Cardiol 15(12):744–756.  https://doi.org/10.1038/s41569-018-0075-z CrossRefPubMedGoogle Scholar
  70. 70.
    de la Torre JC (2012) Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc Psychiatry Neurol 2012:367516.  https://doi.org/10.1155/2012/367516 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    De Silva TM, Faraci FM (2016) Microvascular dysfunction and cognitive impairment. Cell Mol Neurobiol 36(2):241–258.  https://doi.org/10.1007/s10571-015-0308-1 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Ueno M, Sakamoto H, Tomimoto H, Akiguchi I, Onodera M, Huang CL, Kanenishi K (2004) Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats. Acta Neuropathol 107(6):532–538.  https://doi.org/10.1007/s00401-004-0845-z CrossRefPubMedGoogle Scholar
  73. 73.
    Alves TC, Rays J, Fraguas R Jr, Wajngarten M, Meneghetti JC, Prando S, Busatto GF (2005) Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT. J Neuroimaging 15(2):150–156.  https://doi.org/10.1177/1051228404272880 CrossRefPubMedGoogle Scholar
  74. 74.
    Choi BR, Kim JS, Yang YJ, Park KM, Lee CW, Kim YH, Hong MK, Song JK et al (2006) Factors associated with decreased cerebral blood flow in congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 97(9):1365–1369.  https://doi.org/10.1016/j.amjcard.2005.11.059
  75. 75.
    Witt BJ, Gami AS, Ballman KV, Brown RD Jr, Meverden RA, Jacobsen SJ, Roger VL (2007) The incidence of ischemic stroke in chronic heart failure: a meta-analysis. J Cardiac Fail 13(6):489–496.  https://doi.org/10.1016/j.cardfail.2007.01.009 CrossRefGoogle Scholar
  76. 76.
    Marcus NJ, Rio R, Schultz EP, Xia X-H, Schultz HD (2014) Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure. J Physiol 592(Pt 2):391–408.  https://doi.org/10.1113/jphysiol.2013.266221 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Del Rio R, Marcus NJ, Schultz HD (2013) Carotid chemoreceptor ablation improves survival in heart failure: rescuing autonomic control of cardiorespiratory function. J Am Coll Cardiol 62(25):2422–2430.  https://doi.org/10.1016/j.jacc.2013.07.079 CrossRefPubMedGoogle Scholar
  78. 78.
    Toledo C, Andrade DC, Lucero C, Arce-Alvarez A, Díaz HS, Aliaga V, Schultz HD, Marcus NJ et al (2017) Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in HFpEF rats. J Physiol.  https://doi.org/10.1113/JP273558
  79. 79.
    Florea VG, Cohn JN (2014) The autonomic nervous system and heart failure. Circ Res 114(11):1815–1826.  https://doi.org/10.1161/circresaha.114.302589 CrossRefPubMedGoogle Scholar
  80. 80.
    Zucker IH (2006) Novel mechanisms of sympathetic regulation in chronic heart failure. Hypertension (Dallas, Tex : 1979) 48(6):1005–1011.  https://doi.org/10.1161/01.hyp.0000246614.47231.25 CrossRefGoogle Scholar
  81. 81.
    Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohn JN (1984) The neurohumoral axis in congestive heart failure. Ann Intern Med 101(3):370–377CrossRefGoogle Scholar
  82. 82.
    Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM et al (2002) Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 288(17):2144–2150Google Scholar
  83. 83.
    Inestrosa NC, Arenas E (2010) Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 11(2):77–86.  https://doi.org/10.1038/nrn2755 CrossRefPubMedGoogle Scholar
  84. 84.
    Woo MA, Macey PM, Fonarow GC, Hamilton MA, Harper RM (2003) Regional brain gray matter loss in heart failure. J Appl Physiol (Bethesda, Md : 1985) 95(2):677–684.  https://doi.org/10.1152/japplphysiol.00101.2003 CrossRefGoogle Scholar
  85. 85.
    Femminella DG, Candido C, Conte M, Provenzano S, Rengo C, Coscioni E, Ferrara N (2016) Cognitive function and heart failure: the role of the adrenergic system. Recent Pat Endocr, Metab Immune Drug Discovery 10(1):40–49CrossRefGoogle Scholar
  86. 86.
    Esler M, Lambert G, Brunner-La Rocca HP, Vaddadi G, Kaye D (2003) Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice. Acta Physiol Scand 177(3):275–284.  https://doi.org/10.1046/j.1365-201X.2003.01089.x CrossRefPubMedGoogle Scholar
  87. 87.
    Guyenet PG, Haselton JR, Sun MK (1989) Sympathoexcitatory neurons of the rostroventrolateral medulla and the origin of the sympathetic vasomotor tone. Prog Brain Res 81:105–116CrossRefGoogle Scholar
  88. 88.
    Guyenet PG, Stornetta RL, Bochorishvili G, DePuy SD, Burke PGR, Abbott SBG (2013) C1 neurons: the body’s EMTs. Am J Physiol Regul Integr Comp Physiol 305(3):R187–R204.  https://doi.org/10.1152/ajpregu.00054.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Stormer VS, Passow S, Biesenack J, Li SC (2012) Dopaminergic and cholinergic modulations of visual-spatial attention and working memory: insights from molecular genetic research and implications for adult cognitive development. Dev Psychol 48(3):875–889.  https://doi.org/10.1037/a0026198 CrossRefPubMedGoogle Scholar
  90. 90.
    Meel-van den Abeelen AS, Lagro J, Gommer ED, Reulen JP, Claassen JA (2013) Baroreflex function is reduced in Alzheimer’s disease: a candidate biomarker? Neurobiol Aging 34(4):1170–1176.  https://doi.org/10.1016/j.neurobiolaging.2012.10.010 CrossRefPubMedGoogle Scholar
  91. 91.
    Femminella GD, Rengo G, Komici K, Iacotucci P, Petraglia L, Pagano G, de Lucia C, Canonico V et al (2014) Autonomic dysfunction in Alzheimer’s disease: tools for assessment and review of the literature. J Alzheimer’s Dis 42(2):369–377.  https://doi.org/10.3233/jad-140513
  92. 92.
    Zagon A, Totterdell S, Jones RS (1994) Direct projections from the ventrolateral medulla oblongata to the limbic forebrain: anterograde and retrograde tract-tracing studies in the rat. J Comp Neurol 340(4):445–468.  https://doi.org/10.1002/cne.903400402 CrossRefPubMedGoogle Scholar
  93. 93.
    Westerhaus MJ, Loewy AD (2001) Central representation of the sympathetic nervous system in the cerebral cortex. Brain Res 903(1-2):117–127CrossRefGoogle Scholar
  94. 94.
    Hagena H, Hansen N, Manahan-Vaughan D (2016) β-adrenergic control of hippocampal function: subserving the choreography of synaptic information storage and memory. Cereb Cortex (New York, NY : 1991) 26(4):1349–1364.  https://doi.org/10.1093/cercor/bhv330 CrossRefGoogle Scholar
  95. 95.
    Gelinas JN, Tenorio G, Lemon N, Abel T, Nguyen PV (2008) Beta-adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus. Learn Mem (Cold Spring Harbor, NY) 15(5):281–289.  https://doi.org/10.1101/lm.829208 CrossRefGoogle Scholar
  96. 96.
    Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10(3):211–223.  https://doi.org/10.1038/nrn2573 CrossRefPubMedGoogle Scholar
  97. 97.
    Mather M, Harley CW (2016) The locus coeruleus: essential for maintaining cognitive function and the aging brain. Trends Cogn Sci 20(3):214–226.  https://doi.org/10.1016/j.tics.2016.01.001 CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450.  https://doi.org/10.1146/annurev.neuro.28.061604.135709 CrossRefPubMedGoogle Scholar
  99. 99.
    Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42(1):33–84CrossRefGoogle Scholar
  100. 100.
    Kelly SC, He B, Perez SE, Ginsberg SD, Mufson EJ, Counts SE (2017) Locus coeruleus cellular and molecular pathology during the progression of Alzheimer’s disease. Acta Neuropathol Commun 5(1):8.  https://doi.org/10.1186/s40478-017-0411-2 CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Borson S, Barnes RF, Veith RC, Halter JB, Raskind MA (1989) Impaired sympathetic nervous system response to cognitive effort in early Alzheimer’s disease. J Gerontol 44(1):M8–M12Google Scholar
  102. 102.
    Lawlor BA, Bierer LM, Ryan TM, Schmeidler J, Knott PJ, Williams LL, Mohs RC, Davis KL (1995) Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and clinical symptoms in Alzheimer’s disease. Biol Psychiatry 38(3):185–188.  https://doi.org/10.1016/0006-3223(94)00259-6 CrossRefPubMedGoogle Scholar
  103. 103.
    Jett JD, Morilak DA (2013) Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition. Neuropsychopharmacology 38(4):585–595.  https://doi.org/10.1038/npp.2012.216 CrossRefPubMedGoogle Scholar
  104. 104.
    Wang LY, Murphy RR, Hanscom B, Li G, Millard SP, Petrie EC, Galasko DR, Sikkema C et al (2013) Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span. Neurobiol Aging 34(10):2287–2292.  https://doi.org/10.1016/j.neurobiolaging.2013.04.007
  105. 105.
    Abbott SB, Kanbar R, Bochorishvili G, Coates MB, Stornetta RL, Guyenet PG (2012) C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats. J Physiol 590(12):2897–2915.  https://doi.org/10.1113/jphysiol.2012.232157 CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Holloway BB, Viar KE, Stornetta RL, Guyenet PG (2015) The retrotrapezoid nucleus stimulates breathing by releasing glutamate in adult conscious mice. Eur J Neurosci 42(6):2271–2282.  https://doi.org/10.1111/ejn.12996 CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Sara SJ, Vankov A, Hervé A (1994) Locus coeruleus-evoked responses in behaving rats: A clue to the role of noradrenaline in memory. Brain Res Bull 35(5):457–465.  https://doi.org/10.1016/0361-9230(94)90159-7 CrossRefPubMedGoogle Scholar
  108. 108.
    Schwarz LA, Luo L (2015) Organization of the locus coeruleus-norepinephrine system. Curr Biol 25(21):R1051–r1056.  https://doi.org/10.1016/j.cub.2015.09.039 CrossRefPubMedGoogle Scholar
  109. 109.
    Hammerer D, Callaghan MF, Hopkins A, Kosciessa J, Betts M, Cardenas-Blanco A, Kanowski M, Weiskopf N et al (2018) Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events. Proc Natl Acad Sci U S A 115(9):2228–2233.  https://doi.org/10.1073/pnas.1712268115
  110. 110.
    Weinreich P, Seeman P (1981) Binding of adrenergic ligands ([3H]clonidine and [3H]WB-4101) to multiple sites in human brain. Biochem Pharmacol 30(22):3115–3120.  https://doi.org/10.1016/0006-2952(81)90502-5 CrossRefPubMedGoogle Scholar
  111. 111.
    Impey S, Obrietan K, Storm DR (1999) Making new connections: role of ERK/MAP kinase signaling in neuronal plasticity. Neuron 23(1):11–14CrossRefGoogle Scholar
  112. 112.
    Winder DG, Martin KC, Muzzio IA, Rohrer D, Chruscinski A, Kobilka B, Kandel ER (1999) ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors. Neuron 24(3):715–726CrossRefGoogle Scholar
  113. 113.
    Hein L (2006) Adrenoceptors and signal transduction in neurons. Cell Tissue Res 326(2):541–551.  https://doi.org/10.1007/s00441-006-0285-2 CrossRefPubMedGoogle Scholar
  114. 114.
    Daaka Y, Luttrell LM, Lefkowitz RJ (1997) Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature 390(6655):88–91.  https://doi.org/10.1038/36362 CrossRefPubMedGoogle Scholar
  115. 115.
    Zamah AM, Delahunty M, Luttrell LM, Lefkowitz RJ (2002) Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted system. J Biol Chem 277(34):31249–31256.  https://doi.org/10.1074/jbc.M202753200 CrossRefPubMedGoogle Scholar
  116. 116.
    Gurevich VV, Gurevich EV (2006) The structural basis of arrestin-mediated regulation of G-protein-coupled receptors. Pharmacol Ther 110(3):465–502.  https://doi.org/10.1016/j.pharmthera.2005.09.008 CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Lan T-H, Kuravi S, Lambert NA (2011) Internalization dissociates β2-adrenergic receptors. PLoS One 6(2):e17361–e17361.  https://doi.org/10.1371/journal.pone.0017361 CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Rao NP, Danivas V, Venkatasubramanian G, Behere RV, Gangadhar BN (2010) Comorbid bipolar disorder and Usher syndrome. Prim Care Companion J Clin Psychiatry 12(2):PCC.09l00792.  https://doi.org/10.4088/PCC.09l00792yel CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    O’Rourke MF, Iversen LJ, Lomasney JW, Bylund DB (1994) Species orthologs of the alpha-2A adrenergic receptor: the pharmacological properties of the bovine and rat receptors differ from the human and porcine receptors. J Pharmacol Exp Ther 271(2):735–740PubMedGoogle Scholar
  120. 120.
    Birnbaum S, Gobeske KT, Auerbach J, Taylor JR, Arnsten AF (1999) A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry 46(9):1266–1274CrossRefGoogle Scholar
  121. 121.
    Dinh L, Nguyen T, Salgado H, Atzori M (2009) Norepinephrine homogeneously inhibits alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate- (AMPAR-) mediated currents in all layers of the temporal cortex of the rat. Neurochem Res 34(11):1896–1906.  https://doi.org/10.1007/s11064-009-9966-z CrossRefPubMedGoogle Scholar
  122. 122.
    Gelinas JN, Nguyen PV (2005) Beta-adrenergic receptor activation facilitates induction of a protein synthesis-dependent late phase of long-term potentiation. J Neurosci 25(13):3294–3303.  https://doi.org/10.1523/jneurosci.4175-04.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Yu JT, Wang ND, Ma T, Jiang H, Guan J, Tan L (2011) Roles of beta-adrenergic receptors in Alzheimer’s disease: implications for novel therapeutics. Brain Res Bull 84(2):111–117.  https://doi.org/10.1016/j.brainresbull.2010.11.004 CrossRefPubMedGoogle Scholar
  124. 124.
    Cahill L, McGaugh JL (1996) Modulation of memory storage. Curr Opin Neurobiol 6(2):237–242CrossRefGoogle Scholar
  125. 125.
    Soumerai SB, McLaughlin TJ, Spiegelman D, Hertzmark E, Thibault G, Goldman L (1997) Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction. JAMA 277(2):115–121CrossRefGoogle Scholar
  126. 126.
    Luong K, Nguyen LT (2013) The role of Beta-adrenergic receptor blockers in Alzheimer’s disease: potential genetic and cellular signaling mechanisms. Am J Alzheimers Dis Other Dement 28(5):427–439.  https://doi.org/10.1177/1533317513488924 CrossRefGoogle Scholar
  127. 127.
    Shimohama S, Taniguchi T, Fujiwara M, Kameyama M (1987) Changes in beta-adrenergic receptor subtypes in Alzheimer-type dementia. J Neurochem 48(4):1215–1221CrossRefGoogle Scholar
  128. 128.
    Oppenheim G, Mintzer J, Halperin Y, Eliakim R, Stessman J, Ebstein RP (1984) Acute desensitization of lymphocyte beta-adrenergic-stimulated adenylate cyclase in old age and Alzheimer’s disease. Life Sci 35(17):1795–1802CrossRefGoogle Scholar
  129. 129.
    Gliebus G, Lippa CF (2007) The influence of beta-blockers on delayed memory function in people with cognitive impairment. Am J Alzheimers Dis Other Dement 22(1):57–61.  https://doi.org/10.1177/1533317506295889 CrossRefGoogle Scholar
  130. 130.
    Steinman MA, Zullo AR, Lee Y, Daiello LA, Boscardin WJ, Dore DD, Gan S, Fung K et al (2017) Association of beta-blockers with functional outcomes, death, and rehospitalization in older nursing home residents after acute myocardial infarction. JAMA Intern Med 177(2):254–262.  https://doi.org/10.1001/jamainternmed.2016.7701
  131. 131.
    Introini-Collison IB, Miyazaki B, McGaugh JL (1991) Involvement of the amygdala in the memory-enhancing effects of clenbuterol. Psychopharmacology 104(4):541–544CrossRefGoogle Scholar
  132. 132.
    Hecht PM, Will MJ, Schachtman TR, Welby LM, Beversdorf DQ (2014) Beta-adrenergic antagonist effects on a novel cognitive flexibility task in rodents. Behav Brain Res 260:148–154.  https://doi.org/10.1016/j.bbr.2013.11.041 CrossRefPubMedGoogle Scholar
  133. 133.
    Schutsky K, Ouyang M, Thomas SA (2011) Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled beta2-adrenergic signaling. Learn Mem (Cold Spring Harbor, NY) 18(9):598–604.  https://doi.org/10.1101/lm.2302811 CrossRefGoogle Scholar
  134. 134.
    Mirbolooki MR, Constantinescu CC, Pan ML, Mukherjee J (2011) Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation. EJNMMI Res 1(1):30.  https://doi.org/10.1186/2191-219x-1-30 CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Csányi G, Miller Jr FJ (2014) Oxidative stress in cardiovascular disease. Int J Mol Sci 15(4):6002-6008.  https://doi.org/10.3390/ijms15046002
  136. 136.
    Hatanaka H, Hanyu H, Hirose D, Fukusawa R, Namioka N, Iwamoto T (2015) Peripheral oxidative stress markers in individuals with Alzheimer’s disease with or without cerebrovascular disease. J Am Geriatr Soc 63(7):1472–1474.  https://doi.org/10.1111/jgs.13549 CrossRefPubMedGoogle Scholar
  137. 137.
    Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247.  https://doi.org/10.1038/35041687 CrossRefGoogle Scholar
  138. 138.
    Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3(4):431–443.  https://doi.org/10.1016/j.arr.2004.05.002 CrossRefPubMedGoogle Scholar
  139. 139.
    Abd El Mohsen MM, Iravani MM, Spencer JP, Rose S, Fahim AT, Motawi TM, Ismail NA, Jenner P (2005) Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants. Biochem Biophys Res Commun 336(2):386–391.  https://doi.org/10.1016/j.bbrc.2005.07.201 CrossRefPubMedGoogle Scholar
  140. 140.
    Rodrigues Siqueira I, Fochesatto C, da Silva Torres IL, Dalmaz C, Alexandre Netto C (2005) Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats. Life Sci 78(3):271–278.  https://doi.org/10.1016/j.lfs.2005.04.044 CrossRefPubMedGoogle Scholar
  141. 141.
    Zhu Y, Carvey PM, Ling Z (2006) Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res 1090(1):35–44.  https://doi.org/10.1016/j.brainres.2006.03.063 CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Zhang C, Rodriguez C, Spaulding J, Aw TY, Feng J (2012) Age-dependent and tissue-related glutathione redox status in a mouse model of Alzheimer’s disease. J Alzheimer’s Dis 28(3):655–666.  https://doi.org/10.3233/jad-2011-111244 CrossRefGoogle Scholar
  143. 143.
    Hajjar I, Hayek SS, Goldstein FC, Martin G, Jones DP, Quyyumi A (2018) Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J Neuroinflammation 15(1):17.  https://doi.org/10.1186/s12974-017-1026-z CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Palomera-Avalos V, Grinan-Ferre C, Puigoriol-Ilamola D, Camins A, Sanfeliu C, Canudas AM, Pallas M (2017) Resveratrol protects SAMP8 brain under metabolic stress: focus on mitochondrial function and Wnt pathway. Mol Neurobiol 54(3):1661–1676.  https://doi.org/10.1007/s12035-016-9770-0 CrossRefPubMedGoogle Scholar
  145. 145.
    Firoz CK, Jabir NR, Khan MS, Mahmoud M, Shakil S, Damanhouri GA, Zaidi SK, Tabrez S et al (2015) An overview on the correlation of neurological disorders with cardiovascular disease. Saudi J Biol Sci 22(1):19–23.  https://doi.org/10.1016/j.sjbs.2014.09.003
  146. 146.
    Xu B, Li H (2015) Brain mechanisms of sympathetic activation in heart failure: Roles of the renin-angiotensin system, nitric oxide and pro-inflammatory cytokines (Review). Mol Med Rep 12(6):7823–7829.  https://doi.org/10.3892/mmr.2015.4434 CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Lane RK, Hilsabeck T, Rea SL (2015) The role of mitochondrial dysfunction in age-related diseases. Biochim Biophys Acta 1847(11):1387–1400.  https://doi.org/10.1016/j.bbabio.2015.05.021 CrossRefPubMedGoogle Scholar
  148. 148.
    Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintron M, Chen T, Marcinek DJ, Dorn GW 2nd et al (2011) Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circ Res 108(7):837–846.  https://doi.org/10.1161/circresaha.110.232306
  149. 149.
    Foulquier S, Daskalopoulos EP, Lluri G, Hermans KCM, Deb A, Blankesteijn WM (2018) WNT signaling in cardiac and vascular disease. Pharmacol Rev 70(1):68–141.  https://doi.org/10.1124/pr.117.013896 CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart (British Cardiac Society) 90(4):464–470.  https://doi.org/10.1136/hrt.2002.007005 CrossRefGoogle Scholar
  151. 151.
    Adamski MG, Sternak M, Mohaissen T, Kaczor D, Wieronska JM, Malinowska M, Czaban I, Byk K et al (2018) Vascular cognitive impairment linked to brain endothelium inflammation in early stages of heart failure in mice. J Am Heart Assoc 7(7).  https://doi.org/10.1161/jaha.117.007694
  152. 152.
    McColl BW, Rothwell NJ, Allan SM (2008) Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. J Neurosci 28(38):9451–9462.  https://doi.org/10.1523/jneurosci.2674-08.2008 CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Kang Y-M, Gao F, Li H-H, Cardinale JP, Elks C, Zang W-J, Yu X-J, Xu Y-Y et al (2011) NF-κB in the paraventricular nucleus modulates neurotransmitters and contributes to sympathoexcitation in heart failure. Basic Res Cardiol 106(6):1087–1097.  https://doi.org/10.1007/s00395-011-0215-7
  154. 154.
    Kang YM, Zhang ZH, Xue B, Weiss RM, Felder RB (2008) Inhibition of brain proinflammatory cytokine synthesis reduces hypothalamic excitation in rats with ischemia-induced heart failure. Am J Physiol Heart Circ Physiol 295(1):H227–H236.  https://doi.org/10.1152/ajpheart.01157.2007 CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Khacho M, Clark A, Svoboda DS, MacLaurin JG, Lagace DC, Park DS, Slack RS (2017) Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet 26(17):3327–3341.  https://doi.org/10.1093/hmg/ddx217 CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Finsterer J (2012) Cognitive dysfunction in mitochondrial disorders. Acta Neurol Scand 126(1):1–11.  https://doi.org/10.1111/j.1600-0404.2012.01649.x CrossRefPubMedGoogle Scholar
  157. 157.
    Itoh K, Nakamura K, Iijima M, Sesaki H (2013) Mitochondrial dynamics in neurodegeneration. Trends Cell Biol 23(2):64–71.  https://doi.org/10.1016/j.tcb.2012.10.006 CrossRefPubMedGoogle Scholar
  158. 158.
    Chauhan A, Vera J, Wolkenhauer O (2014) The systems biology of mitochondrial fission and fusion and implications for disease and aging. Biogerontology 15(1):1–12.  https://doi.org/10.1007/s10522-013-9474-z CrossRefPubMedGoogle Scholar
  159. 159.
    Golpich M, Amini E, Mohamed Z, Azman Ali R, Mohamed Ibrahim N, Ahmadiani A (2017) Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: pathogenesis and treatment. CNS Neurosci Ther 23(1):5–22.  https://doi.org/10.1111/cns.12655 CrossRefPubMedGoogle Scholar
  160. 160.
    Picard M, McEwen BS (2014) Mitochondria impact brain function and cognition. Proc Natl Acad Sci 111(1):7–8.  https://doi.org/10.1073/pnas.1321881111 CrossRefPubMedGoogle Scholar
  161. 161.
    Giacomello M, Drago I, Pizzo P, Pozzan T (2007) Mitochondrial Ca2+ as a key regulator of cell life and death. Cell Death Differ 14(7):1267–1274.  https://doi.org/10.1038/sj.cdd.4402147 CrossRefPubMedGoogle Scholar
  162. 162.
    Herring BE, Nicoll RA (2016) Long-term potentiation: from camkii to ampa receptor trafficking. Annu Rev Physiol 78:351–365.  https://doi.org/10.1146/annurev-physiol-021014-071753 CrossRefPubMedGoogle Scholar
  163. 163.
    Wang H, Zhang H, Wong YH, Voolstra C, Ravasi T, V BB, Qian PY (2010) Rapid transcriptome and proteome profiling of a non-model marine invertebrate, Bugula neritina. Proteomics 10(16):2972–2981.  https://doi.org/10.1002/pmic.201000056 CrossRefPubMedGoogle Scholar
  164. 164.
    Cerpa W, Gambrill A, Inestrosa NC, Barria A (2011) Regulation of NMDA-receptor synaptic transmission by Wnt signaling. J Neurosci 31(26):9466–9471.  https://doi.org/10.1523/JNEUROSCI.6311-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Oliva CA, Montecinos-Oliva C, Inestrosa NC (2018) Wnt signaling in the central nervous system: new insights in health and disease. Prog Mol Biol Transl Sci 153:81–130.  https://doi.org/10.1016/bs.pmbts.2017.11.018 CrossRefPubMedGoogle Scholar
  166. 166.
    Gillers BS, Chiplunkar A, Aly H, Valenta T, Basler K, Christoffels VM, Efimov IR, Boukens BJ et al (2015) Canonical wnt signaling regulates atrioventricular junction programming and electrophysiological properties. Circ Res 116(3):398–406.  https://doi.org/10.1161/circresaha.116.304731
  167. 167.
    Malekar P, Hagenmueller M, Anyanwu A, Buss S, Streit MR, Weiss CS, Wolf D, Riffel J et al (2010) Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling. Hypertension (Dallas, Tex : 1979) 55(4):939–945.  https://doi.org/10.1161/hypertensionaha.109.141127
  168. 168.
    Cermakova P, Eriksdotter M, Lund LH, Winblad B, Religa P, Religa D (2015) Heart failure and Alzheimer’s disease. J Intern Med 277(4):406–425.  https://doi.org/10.1111/joim.12287 CrossRefPubMedGoogle Scholar
  169. 169.
    Price DL, Sisodia SS, Borchelt DR (1998) Alzheimer disease — when and why? Nat Genet 19:314.  https://doi.org/10.1038/1196 CrossRefPubMedGoogle Scholar
  170. 170.
    Taurin S, Sandbo N, Qin Y, Browning D, Dulin NO (2006) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase. J Biol Chem 281(15):9971–9976.  https://doi.org/10.1074/jbc.M508778200 CrossRefPubMedGoogle Scholar
  171. 171.
    Verheyen EM, Gottardi CJ (2010) Regulation of Wnt/beta-catenin signaling by protein kinases. Dev Dyn 239(1):34–44.  https://doi.org/10.1002/dvdy.22019 CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    Hino S, Tanji C, Nakayama KI, Kikuchi A (2005) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination. Mol Cell Biol 25(20):9063–9072.  https://doi.org/10.1128/mcb.25.20.9063-9072.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    Fang X, Yu SX, Lu Y, Bast RC Jr, Woodgett JR, Mills GB (2000) Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci U S A 97(22):11960–11965.  https://doi.org/10.1073/pnas.220413597 CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Cardiorespiratory Control, Department of PhysiologyPontificia Universidad Católica de ChileSantiagoChile
  2. 2.Center for Aging and Regeneration (CARE-UC)Pontificia Universidad Católica de ChileSantiagoChile
  3. 3.Centro de investigación en fisiología del ejercicioUniversidad MayorSantiagoChile
  4. 4.Centro de Excelencia en Biomedicina de Magallanes (CEBIMA)Universidad de MagallanesPunta ArenasChile

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