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The locus coeruleus in aging and neurodegenerative diseases

Yıl 2024, Cilt: 18 Sayı: 3, 106 - 110, 30.12.2024

Gülşen Deren Yaman , Esra Candar , İbrahim Demirçubuk , Gülgün Şengül

Öz

The locus coeruleus (LC), a prominent neuromelanin-containing nucleus, plays a critical role in the central nervous system by serving as the main source of norepinephrine. First described by Félix Vicq d’Azyr in the 18th century and later identified as a noradrenaline-rich region through fluorescence histochemistry in the 1960s, the LC influences various brain functions, including attention, learning, stress responses, pain modulation, memory, and sleep. This review explores the anatomy, morphology, and neurochemistry of LC neurons, emphasizing their projections and interactions with multiple brain regions such as the cortex, hippocampus, and thalamus. Additionally, we examine the involvement of the LC in the pathophysiology of age-related neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, where significant neuronal loss in the LC correlates with cognitive decline and other clinical symptoms. Understanding the anatomical and functional heterogeneity of LC neurons provides insights into their crucial role in neuromodulation and highlights potential therapeutic targets for neurodegenerative disorders.

Anahtar Kelimeler

brainstem locus coeruleus neurodegenerative diseases norepinephrine

Teşekkür

We thank the Council of Higher Education of Türkiye for supporting Esra Candar under the 100/2000 CoHE Ph.D. Scholarship Program in the field of “Translational Medicine”.

Kaynakça

  • Carlsson A, Falck B, Hillarp NA. Cellular localization of brain monoamines. Acta Physiol Scand Suppl 1962;56:1–28.
  • Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrin, [3H]dopamine and [3H]dopa in various regions of the brain. Neurochem 1966;13:655–69.
  • Dahlström A, Fuxe K. Localization of monoamines in the lower brain stem. Experientia 1964;20:398–9.
  • Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006;80:53–83.
  • Chan-Palay V, Asan E. Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression. J Comp Neurol 1989;287:357–72.
  • Patt S, Gerhard L. A Golgi study of human locus coeruleus in normal brains and in Parkinson’s disease. Neuropathol Appl Neurobiol 1993;19:519–23.
  • Arendt T, Schindler C, Brückner MK, Eschrich K, Bigl V, Zedlick D, Marcova L. Plastic neuronal remodeling is impaired in patients with Alzheimer’s disease carrying apolipoprotein epsilon 4 allele. J Neurosci 1997;17:516–29.
  • Ordway GA, Stockmeier CA, Cason GW, Klimek V. Pharmacology and distribution of norepinephrine transporters in the human locus coeruleus and raphe nuclei. J Neurosci 1997;17:1710–9.
  • Westlund KN, Denney RM, Kochersperger LM, Rose RM, Abell CW. Distinct monoamine oxidase A and B populations in primate brain. Science 1985;230:181–3.
  • Probst A, Cortés R, Palacios JM. Distribution of alpha 2-adrenergic receptors in the human brainstem: an autoradiographic study using [3H]p-aminoclonidine. Eur J Pharmacol 1984;106:477–88.
  • Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, O’Donohue TL. The anatomy of neuropeptide-Y-containing neurons in rat brain. Neuroscience 1985;15:1159–81.
  • Ch’ng JL, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, Tatemoto K, Morrison JF, Polak JM, Bloom SR. Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury. Neuroscience 1985;16:343–54.
  • Fodor M, Görcs TJ, Palkovits M. Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain. Neuroscience 1992;46:891–908. Erratum in: Neuroscience 1992;48:753.
  • Cooper PE, Fernstrom MH, Rorstad OP, Leeman SE, Martin JB. The regional distribution of somatostatin, substance P and neurotensin in human brain. Brain Res 1981;218:219–32.
  • Counts SE, Mufson EJ. Locus coeruleus. In: Mai JK, Paxinos G, editors. The human nervous system. 3rd ed. Philadelphia (PA): Elsevier Academic Press; 2012. p. 425–7.
  • Fernandes P, Regala J, Correia F, Gonçalves-Ferreira AJ. The human locus coeruleus 3-D stereotactic anatomy. Surg Radiol Anat 2012;34:879–85.
  • Sharma Y, Xu T, Graf WM, Fobbs A, Sherwood CC, Hof PR, Allman JM, Manaye KF. Comparative anatomy of the locus coeruleus in humans and nonhuman primates. J Comp Neurol 2010; 518:963–71.
  • Aston-Jones G, Ennis M, Pieribone VA, Nickell WT, Shipley MT. The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 1986;234:734–7.
  • Holloway BB, Stornetta RL, Bochorishvili G, Erisir A, Viar KE, Guyenet PG. Monosynaptic glutamatergic activation of locus coeruleus and other lower brainstem noradrenergic neurons by the C1 cells in mice. J Neurosci 2013;33:18792–805.
  • Kim MA, Lee HS, Lee BY, Waterhouse BD. Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat. Brain Res 2004;1026:56–67.
  • Aston-Jones G, Shipley MT, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, Shiekhattar R, Akaoka H, Drolet G, Astier B, et al. Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res 1991;88:47–75.
  • Saper CB, Stornetta RL. Central autonomic system. In: Paxinos G, editor. The rat nervous system. 4rd ed. San Diego (CA): Elsevier Academic Press; 2015. p. 629–73.
  • Arnsten AF, Goldman-Rakic PS. Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey. Brain Res 1984;306:9–18.
  • Valentino RJ, Page M, Van Bockstaele E, Aston-Jones G. Corticotropin-releasing factor innervation of the locus coeruleus region: distribution of fibers and sources of input. Neuroscience 1992;48:689–705.
  • Zitnik GA. Control of arousal through neuropeptide afferents of the locus coeruleus. Brain Res 2016;1641:338–50.
  • Reyes BA, Zitnik G, Foster C, Van Bockstaele EJ, Valentino RJ. Social stress engages neurochemically-distinct afferents to the rat locus coeruleus depending on coping strategy. eNeuro 2015;2: ENEURO.0042-15.2015.
  • Bergado JA, Frey S, López J, Almaguer-Melian W, Frey JU. Cholinergic afferents to the locus coeruleus and noradrenergic afferents to the medial septum mediate LTP-reinforcement in the dentate gyrus by stimulation of the amygdala. Neurobiol Learn Mem 2007;88:331–41.
  • Suárez-Pereira I, Llorca-Torralba M, Bravo L, Camarena-Delgado C, Soriano-Mas C, Berrocoso E. The role of the locus coeruleus in pain and associated stress-related disorders. Biol Psychiatry 2022;91:786–97.
  • Waterhouse BD, Devilbiss D, Fleischer D, Sessler FM, Simpson KL. New perspectives on the functional organization and postsynaptic influences of the locus ceruleus efferent projection system. Adv Pharmacol 1998;42:749–54.
  • Foote SL, Morrison JH. Extrathalamic modulation of cortical function. Annu Rev Neurosci 1987;10:67–95.
  • Loughlin SE, Foote SL, Bloom FE. Efferent projections of nucleus locus coeruleus: topographic organization of cells of origin demonstrated by three-dimensional reconstruction. Neuroscience 1986;18:291–306.
  • Morrison JH, Foote SL. Noradrenergic and serotoninergic innervation of cortical, thalamic, and tectal visual structures in old and new world monkeys. J Comp Neurol 1986;243:117–38.
  • Vogt BA, Hof PR, Friedman DP, Sikes RW, Vogt LJ. Norepinephrinergic afferents and cytology of the macaque monkey midline, mediodorsal, and intralaminar thalamic nuclei. Brain Struct Funct 2008;212:465–79.
  • Ginsberg SD, Hof PR, Young WG, Morrison JH. Noradrenergic innervation of the hypothalamus of rhesus monkeys: distribution of dopamine-beta-hydroxylase immunoreactive fibers and quantitative analysis of varicosities in the paraventricular nucleus. J Comp Neurol 1993;327:597–611.
  • Arnsten AF. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 2009;10:410–22.
  • Marcyniuk B, Mann DM, Yates PO. The topography of nerve cell loss from the locus caeruleus in elderly persons. Neurobiol Aging 1989;10:5–9.
  • Manaye KF, McIntire DD, Mann DM, German DC. Locus coeruleus cell loss in the aging human brain: a non-random process. J Comp Neurol 1995;358:79–87.
  • Bondareff W, Mountjoy CQ, Roth M. Selective loss of neurones of origin of adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Lancet 1981;1:783–4.
  • Mann DM, Yates PO, Hawkes J. The pathology of the human locus ceruleus. Clin Neuropathol 1983;2:1–7.
  • Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989;112:1171–92.
  • Kosaka K. Dementia and neuropathology in Lewy body disease. Adv Neurol 1993;60:456–63.
  • Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 2003;60:337–41.
  • German DC, Manaye KF, White CL 3rd, Woodward DJ, McIntire DD, Smith WK, Kalaria RN, Mann DM. Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 1992;32:667–76.
  • Mann DM, Yates PO, Marcyniuk B. A comparison of changes in the nucleus basalis and locus coeruleus in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1984;47:201–3.
  • Förstl H, Levy R, Burns A, Luthert P, Cairns N. Disproportionate loss of noradrenergic and cholinergic neurons as cause of depression in Alzheimer’s disease-a hypothesis. Pharmacopsychiatry 1994;27:11–5.

Yıl 2024, Cilt: 18 Sayı: 3, 106 - 110, 30.12.2024

Gülşen Deren Yaman , Esra Candar , İbrahim Demirçubuk , Gülgün Şengül

Öz

Kaynakça

  • Carlsson A, Falck B, Hillarp NA. Cellular localization of brain monoamines. Acta Physiol Scand Suppl 1962;56:1–28.
  • Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrin, [3H]dopamine and [3H]dopa in various regions of the brain. Neurochem 1966;13:655–69.
  • Dahlström A, Fuxe K. Localization of monoamines in the lower brain stem. Experientia 1964;20:398–9.
  • Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006;80:53–83.
  • Chan-Palay V, Asan E. Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression. J Comp Neurol 1989;287:357–72.
  • Patt S, Gerhard L. A Golgi study of human locus coeruleus in normal brains and in Parkinson’s disease. Neuropathol Appl Neurobiol 1993;19:519–23.
  • Arendt T, Schindler C, Brückner MK, Eschrich K, Bigl V, Zedlick D, Marcova L. Plastic neuronal remodeling is impaired in patients with Alzheimer’s disease carrying apolipoprotein epsilon 4 allele. J Neurosci 1997;17:516–29.
  • Ordway GA, Stockmeier CA, Cason GW, Klimek V. Pharmacology and distribution of norepinephrine transporters in the human locus coeruleus and raphe nuclei. J Neurosci 1997;17:1710–9.
  • Westlund KN, Denney RM, Kochersperger LM, Rose RM, Abell CW. Distinct monoamine oxidase A and B populations in primate brain. Science 1985;230:181–3.
  • Probst A, Cortés R, Palacios JM. Distribution of alpha 2-adrenergic receptors in the human brainstem: an autoradiographic study using [3H]p-aminoclonidine. Eur J Pharmacol 1984;106:477–88.
  • Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, O’Donohue TL. The anatomy of neuropeptide-Y-containing neurons in rat brain. Neuroscience 1985;15:1159–81.
  • Ch’ng JL, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, Tatemoto K, Morrison JF, Polak JM, Bloom SR. Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury. Neuroscience 1985;16:343–54.
  • Fodor M, Görcs TJ, Palkovits M. Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain. Neuroscience 1992;46:891–908. Erratum in: Neuroscience 1992;48:753.
  • Cooper PE, Fernstrom MH, Rorstad OP, Leeman SE, Martin JB. The regional distribution of somatostatin, substance P and neurotensin in human brain. Brain Res 1981;218:219–32.
  • Counts SE, Mufson EJ. Locus coeruleus. In: Mai JK, Paxinos G, editors. The human nervous system. 3rd ed. Philadelphia (PA): Elsevier Academic Press; 2012. p. 425–7.
  • Fernandes P, Regala J, Correia F, Gonçalves-Ferreira AJ. The human locus coeruleus 3-D stereotactic anatomy. Surg Radiol Anat 2012;34:879–85.
  • Sharma Y, Xu T, Graf WM, Fobbs A, Sherwood CC, Hof PR, Allman JM, Manaye KF. Comparative anatomy of the locus coeruleus in humans and nonhuman primates. J Comp Neurol 2010; 518:963–71.
  • Aston-Jones G, Ennis M, Pieribone VA, Nickell WT, Shipley MT. The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 1986;234:734–7.
  • Holloway BB, Stornetta RL, Bochorishvili G, Erisir A, Viar KE, Guyenet PG. Monosynaptic glutamatergic activation of locus coeruleus and other lower brainstem noradrenergic neurons by the C1 cells in mice. J Neurosci 2013;33:18792–805.
  • Kim MA, Lee HS, Lee BY, Waterhouse BD. Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat. Brain Res 2004;1026:56–67.
  • Aston-Jones G, Shipley MT, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, Shiekhattar R, Akaoka H, Drolet G, Astier B, et al. Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res 1991;88:47–75.
  • Saper CB, Stornetta RL. Central autonomic system. In: Paxinos G, editor. The rat nervous system. 4rd ed. San Diego (CA): Elsevier Academic Press; 2015. p. 629–73.
  • Arnsten AF, Goldman-Rakic PS. Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey. Brain Res 1984;306:9–18.
  • Valentino RJ, Page M, Van Bockstaele E, Aston-Jones G. Corticotropin-releasing factor innervation of the locus coeruleus region: distribution of fibers and sources of input. Neuroscience 1992;48:689–705.
  • Zitnik GA. Control of arousal through neuropeptide afferents of the locus coeruleus. Brain Res 2016;1641:338–50.
  • Reyes BA, Zitnik G, Foster C, Van Bockstaele EJ, Valentino RJ. Social stress engages neurochemically-distinct afferents to the rat locus coeruleus depending on coping strategy. eNeuro 2015;2: ENEURO.0042-15.2015.
  • Bergado JA, Frey S, López J, Almaguer-Melian W, Frey JU. Cholinergic afferents to the locus coeruleus and noradrenergic afferents to the medial septum mediate LTP-reinforcement in the dentate gyrus by stimulation of the amygdala. Neurobiol Learn Mem 2007;88:331–41.
  • Suárez-Pereira I, Llorca-Torralba M, Bravo L, Camarena-Delgado C, Soriano-Mas C, Berrocoso E. The role of the locus coeruleus in pain and associated stress-related disorders. Biol Psychiatry 2022;91:786–97.
  • Waterhouse BD, Devilbiss D, Fleischer D, Sessler FM, Simpson KL. New perspectives on the functional organization and postsynaptic influences of the locus ceruleus efferent projection system. Adv Pharmacol 1998;42:749–54.
  • Foote SL, Morrison JH. Extrathalamic modulation of cortical function. Annu Rev Neurosci 1987;10:67–95.
  • Loughlin SE, Foote SL, Bloom FE. Efferent projections of nucleus locus coeruleus: topographic organization of cells of origin demonstrated by three-dimensional reconstruction. Neuroscience 1986;18:291–306.
  • Morrison JH, Foote SL. Noradrenergic and serotoninergic innervation of cortical, thalamic, and tectal visual structures in old and new world monkeys. J Comp Neurol 1986;243:117–38.
  • Vogt BA, Hof PR, Friedman DP, Sikes RW, Vogt LJ. Norepinephrinergic afferents and cytology of the macaque monkey midline, mediodorsal, and intralaminar thalamic nuclei. Brain Struct Funct 2008;212:465–79.
  • Ginsberg SD, Hof PR, Young WG, Morrison JH. Noradrenergic innervation of the hypothalamus of rhesus monkeys: distribution of dopamine-beta-hydroxylase immunoreactive fibers and quantitative analysis of varicosities in the paraventricular nucleus. J Comp Neurol 1993;327:597–611.
  • Arnsten AF. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 2009;10:410–22.
  • Marcyniuk B, Mann DM, Yates PO. The topography of nerve cell loss from the locus caeruleus in elderly persons. Neurobiol Aging 1989;10:5–9.
  • Manaye KF, McIntire DD, Mann DM, German DC. Locus coeruleus cell loss in the aging human brain: a non-random process. J Comp Neurol 1995;358:79–87.
  • Bondareff W, Mountjoy CQ, Roth M. Selective loss of neurones of origin of adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Lancet 1981;1:783–4.
  • Mann DM, Yates PO, Hawkes J. The pathology of the human locus ceruleus. Clin Neuropathol 1983;2:1–7.
  • Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989;112:1171–92.
  • Kosaka K. Dementia and neuropathology in Lewy body disease. Adv Neurol 1993;60:456–63.
  • Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 2003;60:337–41.
  • German DC, Manaye KF, White CL 3rd, Woodward DJ, McIntire DD, Smith WK, Kalaria RN, Mann DM. Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 1992;32:667–76.
  • Mann DM, Yates PO, Marcyniuk B. A comparison of changes in the nucleus basalis and locus coeruleus in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1984;47:201–3.
  • Förstl H, Levy R, Burns A, Luthert P, Cairns N. Disproportionate loss of noradrenergic and cholinergic neurons as cause of depression in Alzheimer’s disease-a hypothesis. Pharmacopsychiatry 1994;27:11–5.
Toplam 45 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hücresel Sinir Sistemi, Merkezi Sinir Sistemi
Bölüm Reviews
Yazarlar

Gülşen Deren Yaman 0009-0001-6638-3505

Esra Candar 0000-0001-5408-5570

İbrahim Demirçubuk 0000-0002-6574-9587

Gülgün Şengül 0000-0002-5826-7379

Yayımlanma Tarihi 30 Aralık 2024
Gönderilme Tarihi 27 Ağustos 2024
Kabul Tarihi 28 Kasım 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 18 Sayı: 3

Kaynak Göster

APA Yaman, G. D., Candar, E., Demirçubuk, İ., Şengül, G. (2024). The locus coeruleus in aging and neurodegenerative diseases. Anatomy, 18(3), 106-110.
AMA Yaman GD, Candar E, Demirçubuk İ, Şengül G. The locus coeruleus in aging and neurodegenerative diseases. Anatomy. Aralık 2024;18(3):106-110.
Chicago Yaman, Gülşen Deren, Esra Candar, İbrahim Demirçubuk, ve Gülgün Şengül. “The Locus Coeruleus in Aging and Neurodegenerative Diseases”. Anatomy 18, sy. 3 (Aralık 2024): 106-10.
EndNote Yaman GD, Candar E, Demirçubuk İ, Şengül G (01 Aralık 2024) The locus coeruleus in aging and neurodegenerative diseases. Anatomy 18 3 106–110.
IEEE G. D. Yaman, E. Candar, İ. Demirçubuk, ve G. Şengül, “The locus coeruleus in aging and neurodegenerative diseases”, Anatomy, c. 18, sy. 3, ss. 106–110, 2024.
ISNAD Yaman, Gülşen Deren vd. “The Locus Coeruleus in Aging and Neurodegenerative Diseases”. Anatomy 18/3 (Aralık 2024), 106-110.
JAMA Yaman GD, Candar E, Demirçubuk İ, Şengül G. The locus coeruleus in aging and neurodegenerative diseases. Anatomy. 2024;18:106–110.
MLA Yaman, Gülşen Deren vd. “The Locus Coeruleus in Aging and Neurodegenerative Diseases”. Anatomy, c. 18, sy. 3, 2024, ss. 106-10.
Vancouver Yaman GD, Candar E, Demirçubuk İ, Şengül G. The locus coeruleus in aging and neurodegenerative diseases. Anatomy. 2024;18(3):106-10.
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