본문 바로가기
KERD
논문KCI 등재

Orexin and Alzheimer’s Disease: A New Perspective

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류정신과학

초록

Orexin’s role in human cognition has recently been emphasized and emerging evidences indicate its close relationship with Alzheimer’s disease (AD). This review aimed to demonstrate recent research on the relationship between orexin and AD. Orexin’s role in stress regulation and memory is discussed, with significant findings related to sexual disparities in stress response, with potential clinical implications pertaining to AD pathology. There are controversies regarding the orexin levels in AD patients, but the role of orexin in the trajectory of AD is still emphasized in recent literatures. Orexin is also accentuated in the context of tau pathology, and orexin as a potential therapeutic target for AD is frequently discussed. Future directions with regard to the relationship between orexin and AD are suggested: 1) consideration for AD trajectory in the measurement of orexin levels, 2) the need for objective measure such as polysomnography and actigraphy, 3) the need for close observation of cognitive profiles of orexin-deficient narcolepsy patients, 4) the need for validation studies by neuroimaging 5) the need for taking account sexual disparities in orexinergic activiation, and 6) consideration for orexin’s role as a stress regulator. The aforementioned new perspectives could help unravel the relationship between orexin and AD.

Abstract

Orexin’s role in human cognition has recently been emphasized and emerging evidences indicate its close relationship with Alzheimer’s disease (AD). This review aimed to demonstrate recent research on the relationship between orexin and AD. Orexin’s role in stress regulation and memory is discussed, with significant findings related to sexual disparities in stress response, with potential clinical implications pertaining to AD pathology. There are controversies regarding the orexin levels in AD patients, but the role of orexin in the trajectory of AD is still emphasized in recent literatures. Orexin is also accentuated in the context of tau pathology, and orexin as a potential therapeutic target for AD is frequently discussed. Future directions with regard to the relationship between orexin and AD are suggested: 1) consideration for AD trajectory in the measurement of orexin levels, 2) the need for objective measure such as polysomnography and actigraphy, 3) the need for close observation of cognitive profiles of orexin-deficient narcolepsy patients, 4) the need for validation studies by neuroimaging 5) the need for taking account sexual disparities in orexinergic activiation, and 6) consideration for orexin’s role as a stress regulator. The aforementioned new perspectives could help unravel the relationship between orexin and AD.

참고문헌 (80)

  1. Willie JT, "To eat or to sleep? Orexin in the regulation of feeding and wakefulness", Annu Rev Neurosci, 24, pp.429~458 (2001)
  2. Burdakov D, "How orexin signals bias action : hypothalamic and accumbal circuits", Brain Res, 1731, pp.145943~ (2020)
  3. Mavanji V, "Promotion of wakefulness and energy expenditure by orexin-A in the ventrolateral preoptic area", Sleep, 38, pp.1361~1370 (2015)
  4. Prober DA, "Discovery of hypocretin", orexin ushers in a new era of sleep research, 2018, pp.41, 70~72
  5. Soya S, "Orexin as a modulator of fear-related behavior : hypothalamic control of noradrenaline circuit", Brain Res, 1731, pp.146037~ (2020)
  6. Summers CH, "Orexin", hypocretin receptor modulation of anxiolytic and antidepressive responses during social stress and decision-making : Potential for therapy, 2020, pp.1731, 146085~
  7. Burdakov D, "Reactive and predictive homeostasis : roles of orexin", hypocretin neurons, 2019, pp.154, 61~67
  8. Song J, "The role of orexin in post-stroke inflammation, cognitive decline, and depression", Mol Brain, 8, pp.16~ (2015)
  9. Chen Q, "The hypocretin", orexin system : an increasingly important role in neuropsychiatry, 2015, pp.35, 152~197
  10. Grafe LA, "Orexins and stress", Front Neuroendocrinol, 51, pp.132~145 (2018)
  11. Ji MJ, "Orexin prevents depressivelike behavior by promoting stress resilience", Mol Psychiatry, 24, pp.282~293 (2019)
  12. Sargin D, "The role of the orexin system in stress response", Neuropharmacology, 154, pp.68~78 (2019)
  13. Eacret D, "Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory", Behav Brain Res, 356, pp.444~452 (2019)
  14. Bahramzadeh Zoeram S, "Hippocampal orexin receptor blocking prevented the stress induced social learning and memory deficits", Neurobiol Learn Mem, 157, pp.12~23 (2019)
  15. Grafe LA, "Orexins mediate sex differences in the stress response and in cognitive flexibility", Biol Psychiatry, 81, pp.683~692 (2017)
  16. Al-Barazanji KA, "Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats", J Neuroendocrinol, 13, pp.421~424 (2001)
  17. Chang H, "Inhibitory effects of an orexin-2 receptor antagonist on orexin A-and stress-induced ACTH responses in conscious rats", Neurosci Res, 57, pp.462~466 (2007)
  18. Grafe LA, "Reduced orexin system function contributes to resilience to repeated social stress", eNeuro, 5 (2018)
  19. Gozzi A, "Differential effect of orexin-1 and CRF-1 antagonism on stress circuits : a fMRI study in the rat with the pharmacological stressor Yohimbine", Neuropsychopharmacology, 38, pp.2120~2130 (2013)
  20. Walling SG, "Orexin-A infusion in the locus ceruleus triggers norepinephrine(NE)release and NE-induced long-term potentiation in the dentate gyrus", J Neurosci, 24, pp.7421~7426 (2004)
  21. Ardeshiri MR, "Orexin 1 and orexin 2 receptor antagonism in the basolateral amygdala modulate long-term potentiation of the population spike in the perforant path-dentate gyrus-evoked field potential in rats", Neurobiol Learn Mem, 149, pp.98~106 (2018)
  22. Shi L, "Orexin A differentially influences the extinction retention of recent and remote fear memory", Front Neurosci, 12, pp.295~ (2018)
  23. Dang R, "Orexin knockout mice exhibit impaired spatial working memory", Neurosci Lett, 668, pp.92~97 (2018)
  24. Akbari E, "The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze", Peptides, 28, pp.650~656 (2007)
  25. Baykal S, "Decreased serum orexin A levels in drug-naive children with attention deficit and hyperactivity disorder", Neurol Sci, 40, pp.593~602 (2019)
  26. Blake MG, "Basal forebrain cholinergic system and memory", Curr Top Behav Neurosci, 37, pp.253~273 (2018)
  27. Fadel J, "Orexin", hypocretin modulation of the basal forebrain cholinergic system : role in attention, 2010, pp.1314, 112~123
  28. Fadel J, "Orexin", hypocretin modulation of the basal forebrain cholinergic system : insights from in vivo microdialysis studies, 2008, pp.90, 156~162
  29. Ishibashi M, "Orexin receptor activation generates gamma band input to cholinergic and serotonergic arousal system neurons and drives an intrinsic Ca(2+)-dependent resonance in LDT and PPT cholinergic neurons", Front Neurol, 6, pp.120~ (2015)
  30. Stanley EM, "Aging-related deficits in orexin", hypocretin modulation of the septohippocampal cholinergic system, 2012, pp.66, 445~452
  31. Piantadosi PT, "Orexin receptor activity in the basal forebrain alters performance on an olfactory discrimination task", Brain Res, 1594, pp.215~222 (2015)
  32. Cole S, "Medial prefrontal cortex neural plasticity, orexin receptor 1 signaling, and connectivity with the lateral hypothalamus are necessary in cue-potentiated feeding", J Neurosci, 40, pp.1744~1755 (2020)
  33. Duffy CM, "High fat diet increases cognitive decline and neuroinflammation in a model of orexin loss", Neurobiol Learn Mem, 157, pp.41~47 (2019)
  34. Huang H, "Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin : a feedforward circuit that may enhance cognitive arousal", J Neurophysiol, 95, pp.1656~1668 (2006)
  35. Vittoz NM, "Hypocretin", orexin selectively increases dopamine efflux within the prefrontal cortex : involvement of the ventral tegmental area, 2006, pp.31, 384~395
  36. Vittoz NM, "Hypocretin", orexin preferentially activates caudomedial ventral tegmental area dopamine neurons, 2008, pp.28, 1629~1640
  37. Kessler BA, "Age-related loss of orexin", hypocretin neurons, 2011, pp.178, 82~88
  38. Fadel JR, "Food for thought : the role of appetitive peptides in age-related cognitive decline", Ageing Res Rev, 12, pp.764~776 (2013)
  39. Villa C, "The synergistic relationship between Alzheimer’s disease and sleep disorders : an update", J Alzheimers Dis, 46, pp.571~580 (2015)
  40. Lucey BP, "How amyloid, sleep and memory connect", Nat Neurosci, 18, pp.933~934 (2015)
  41. Fronczek R, "Hypocretin(orexin)loss in Alzheimer’s disease", Neurobiol Aging, 33, pp.1642~1650 (2012)
  42. Liguori C, "Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease", JAMA Neurol, 71, pp.1498~1505 (2014)
  43. Roh JH, "Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease", J Exp Med, 211, pp.2487~2496 (2014)
  44. Schmidt FM, "Cerebrospinal fluid melanin-concentrating hormone(MCH)and hypocretin-1(HCRT-1, orexin-A)in Alzheimer’s disease", PLoS One, 8, pp.e63136~ (2013)
  45. Slats D, "Association between hypocretin-1 and amyloid-β42 cerebrospinal fluid levels in Alzheimer’s disease and healthy controls", Curr Alzheimer Res, 9, pp.1119~1125 (2012)
  46. Olsson M, "Sleep deprivation and cerebrospinal fluid biomarkers for Alzheimer’s disease", Sleep, 41 (2018)
  47. Erik S Musiek, "Sleep, circadian rhythms, and the pathogenesis of Alzheimer Disease", Experimental and Molecular Medicine, 47, pp.1~8 (2015), 생화학분자생물학회
  48. Van Egroo M, "Sleep-wake regulation and the hallmarks of the pathogenesis of Alzheimer’s disease", Sleep, 42, pp.pii:zsz017~ (2019)
  49. Ma Z, "Orexin signaling regulates both the hippocampal clock and the circadian oscillation of Alzheimer’s disease-risk genes", Sci Rep, 6, pp.36035~ (2016)
  50. Liguori C, "Orexin and Alzheimer’s disease", Curr Top Behav Neurosci, 33, pp.305~322 (2017)
  51. Kang JE, "Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle", Science, 326, pp.1005~1007 (2009)
  52. An H, "Orexin impairs the phagocytosis and degradation of amyloid-beta fibrils by microglial cells", J Alzheimers Dis, 58, pp.253~261 (2017)
  53. Holth J, "Sleep in Alzheimer’s disease-beyond amyloid", Neurobiol Sleep Circadian Rhythms, 2, pp.4~14 (2017)
  54. Liu Z, "Amyloid β and tau are involved in sleep disorder in Alzheimer’s disease by orexin A and adenosine A(1)receptor", Int J Mol Med, 43, pp.435~442 (2019)
  55. Li M, "Orexin-A exacerbates Alzheimer’s disease by inducing mitochondrial impairment", Neurosci Lett, 718, pp.134741~ (2020)
  56. Gallone S, "Is HCRTR2 a genetic risk factor for Alzheimer’s disease", Dement Geriatr Cogn Disord, 38, pp.245~253 (2014)
  57. Peineau S, "Synaptic plasticity modulation by circulating peptides and metaplasticity : involvement in Alzheimer’s disease", Pharmacol Res, 130, pp.385~401 (2018)
  58. Arias-Carrion O, "Depletion of hypocretin", orexin neurons increases cell proliferation in the adult subventricular zone, 2018, pp.17, 106~112
  59. Roh J, "Gene Therapy in Neurological Disorders", pp.163~175 (2018), Elsevier, Academic Press
  60. Calva CB, "Intranasal administration of orexin peptides : mechanisms and therapeutic potential for age-related cognitive dysfunction", Brain Res, 1731, pp.145921~ (2020)
  61. Lleó A, "Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer’s disease continuum in the BIOMARKAPD study", Alzheimers Dement, 15, pp.742~753 (2019)
  62. Lin L, "The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin(orexin)receptor 2 gene", Cell, 98, pp.365~376 (1999)
  63. Kornum BR, "Narcolepsy with hypocretin", orexin deficiency, infections and autoimmunity of the brain, 2011, pp.21, 897~903
  64. Gabelle A, "Reduced brain amyloid burden in elderly patients with narcolepsy type 1", Ann Neurol, 85, pp.74~83 (2019)
  65. Jennum PJ, "Cerebrospinal fluid biomarkers of neurodegeneration are decreased or normal in narcolepsy", Sleep, 40 (2017)
  66. Hansson O, "CSF biomarkers of Alzheimer’s disease concord with amyloid-βPET and predict clinical progression : a study of fully automated immunoassays in BioFINDER and ADNI cohorts", Alzheimers Dement, 14, pp.1470~1481 (2018)
  67. Jiyoung Lyu, "Gender-Specific Incidence and Predictors of Cognitive Impairment among Older Koreans: Findings from a 6-Year Prospective Cohort Study", PSYCHIATRY INVESTIGATION, 13(5), pp.473~479 (2016), 대한신경정신의학회[DOI]
  68. Wang C, "Estrogen receptor-α is localized to neurofibrillary tangles in Alzheimer’s disease", Sci Rep, 6, pp.20352~ (2016)
  69. Pike CJ, "Sex and the development of Alzheimer’s disease", J Neurosci Res, 95, pp.671~680 (2017)
  70. Merlo S, "Estrogen and Alzheimer’s disease : still an attractive topic despite disappointment from early clinical results", Eur J Pharmacol, 817, pp.51~58 (2017)
  71. Tansupswatdikul P, "Effects of estrogen therapy on postmenopausal sleep quality regardless of vasomotor symptoms : a randomized trial", Climacteric, 18, pp.198~204 (2015)
  72. Joffe H, "Independent contributions of nocturnal hot flashes and sleep disturbance to depression in estrogen-deprived women", J Clin Endocrinol Metab, 101, pp.3847~3855 (2016)
  73. Gervais NJ, "Ovarian hormones, sleep and cognition across the adult female lifespan : an integrated perspective", Front Neuroendocrinol, 47, pp.134~153 (2017)
  74. McHill AW, "The relationship between estrogen and the decline in delta power during adolescence", Sleep, 40 (2017)
  75. El-Sedeek M, "Plasma orexin-A levels in postmenopausal women : possible interaction with estrogen and correlation with cardiovascular risk status", BJOG, 117, pp.488~492 (2010)
  76. Macedo AC, "Is sleep disruption a risk factor for Alzheimer’s disease?", J Alzheimers Dis, 58, pp.993~1002 (2017)
  77. Minakawa EN, "Sleep disturbance as a potential modifiable risk factor for Alzheimer’s disease", Int J Mol Sci, 20, pp.pii: E803~ (2019)
  78. Spira AP, "Sleep disturbance: an emerging opportunity for Alzheimer’s disease prevention?", Int Psychogeriatr, 29, pp.529~531 (2017)
  79. Shi L, "Sleep disturbances increase the risk of dementia : a systematic review and meta-analysis", Sleep Med Rev, 40, pp.4~16 (2018)
  80. Mander BA, "Sleep: a novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer’s disease?", Trends Neurosci, 39, pp.552~566 (2016)

관련 논문AI추천

이 간행물의 다른 논문 (13건)