Activated Wake Systems in Narcolepsy Type 1.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
27
06
2023
received:
06
02
2023
accepted:
29
06
2023
medline:
23
10
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
ppublish
Résumé
Narcolepsy type 1 (NT1) is assumed to be caused solely by a lack of hypocretin (orexin) neurotransmission. Recently, however, we found an 88% reduction in corticotropin-releasing hormone (CRH)-positive neurons in the paraventricular nucleus (PVN). We assessed the remaining CRH neurons in NT1 to determine whether they co-express vasopressin (AVP) to reflect upregulation. We also systematically assessed other wake-systems, since current NT1 treatments target histamine, dopamine, and norepinephrine pathways. In postmortem tissue of people with NT1 and matched controls, we immunohistochemically stained and quantified neuronal populations expressing: CRH and AVP in the PVN, and CRH in the Barrington nucleus; the key neuronal histamine-synthesizing enzyme, histidine decarboxylase (HDC) in the hypothalamic tuberomammillary nucleus (TMN); the rate-limited-synthesizing enzyme, tyrosine hydroxylase (TH), for dopamine in the mid-brain and for norepinephrine in the locus coeruleus (LC). In NT1, there was: a 234% increase in the percentage of CRH cells co-expressing AVP, while there was an unchanged integrated optical density of CRH staining in the Barrington nucleus; a 36% increased number of histamine neurons expressing HDC, while the number of typical human TMN neuronal profiles was unchanged; a tendency toward an increased density of TH-positive neurons in the substantia nigra compacta; while the density of TH-positive LC neurons was unchanged. Our findings suggest an upregulation of activity by histamine neurons and remaining CRH neurons in NT1. This may explain earlier reports of normal basal plasma cortisol levels but lower levels after dexamethasone suppression. Alternatively, CRH neurons co-expressing AVP neurons are less vulnerable. ANN NEUROL 2023;94:762-771.
Substances chimiques
Arginine Vasopressin
113-79-1
Dopamine
VTD58H1Z2X
Histamine
820484N8I3
Corticotropin-Releasing Hormone
9015-71-8
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
762-771Informations de copyright
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Bassetti CLA, Adamantidis A, Burdakov D, et al. Narcolepsy-clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol 2019;15:519-539.
Peyron C, Faraco J, Rogers W, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 2000;6:991-997.
Thannickal TC, Moore RY, Nienhuis R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000;27:469-474.
Mignot E, Lammers GJ, Ripley B, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002;59:1553-1562.
Crocker A, Espana RA, Papadopoulou M, et al. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Neurology 2005;65:1184-1188.
Blouin AM, Thannickal TC, Worley PF, et al. Narp immunostaining of human hypocretin (orexin) neurons: loss in narcolepsy. Neurology 2005;65:1189-1192.
Honda M, Arai T, Fukazawa M, et al. Absence of ubiquitinated inclusions in hypocretin neurons of patients with narcolepsy. Neurology 2009;73:511-517.
Shan L, Balesar R, Swaab DF, et al. Reduced numbers of corticotropin-releasing hormone neurons in narcolepsy type 1. Ann. Neurol. 2022;91:282-288. [cited 2022 Feb 15].
Kok SW, Roelfsema F, Overeem S, et al. Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker. J Clin Endocrinol Metab 2002;87:5085-5091.
Raadsheer FC, Tilders FJH, Swaab DF. Similar age related increase of vasopressin colocalization in paraventricular corticotropin-releasing hormone neurons in controls and Alzheimer patients. J. Neuroendocrinol. 1994;6:131-133. [cited 2022 Jun 2].
Wang SS, Kamphuis W, Huitinga I, et al. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol Psychiatry 2008;13:741-799.
Raadsheer FC, Hoogendijk WJG, Stam FC, et al. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994;60:436-444. [cited 2022 Jun 2].
Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, et al. Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression. Am J Psychiatry 1995;152:1372-1376.
Huitinga I, Erkut ZA, Van Beurden D, Swaab DF. Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions. Ann. Neurol. 2004;55:37-45. [cited 2020 Oct 8].
Melief J, De Wit SJ, Van Eden CG, et al. HPA axis activity in multiple sclerosis correlates with disease severity, lesion type and gene expression in normal-appearing white matter. Acta Neuropathol. 2013;126:237-249. [cited 2020 Oct 30].
John J, Thannickal TC, McGregor R, et al. Greatly increased numbers of histamine cells in human narcolepsy with cataplexy. Ann Neurol 2013;74:786-793.
Valko PO, Gavrilov YV, Yamamoto M, et al. Increase of histaminergic tuberomammillary neurons in narcolepsy. Ann Neurol 2013;74:794-804.
Blanco L, Yuste JE, Carrillo-de Sauvage MA, et al. Critical evaluation of the anatomical location of the Barrington nucleus: relevance for deep brain stimulation surgery of pedunculopontine tegmental nucleus. Neuroscience 2013;247:351-363. [cited 2022 Apr 20].
Dauvilliers Y, Bassetti C, Lammers GJ, et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol 2013;12:1068-1075.
Baladi MG, Forster MJ, Gatch MB, et al. Characterization of the neurochemical and behavioral effects of Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor. J. Pharmacol. Exp. Ther. J Pharmacol Exp Ther 2018;366:367-376. [cited 2020 Mar 30].
Klioueva NM, Rademaker MC, Dexter DT, et al. BrainNet Europe's code of conduct for brain banking. J Neural Transm 2015;122:937-940.
Klioueva NM, Rademaker MC, Huitinga I. Design of a European code of conduct for brain banking. In: Huitinga I, Webster MJBT-H of CN, eds. Brain Banking. Amsterdam: Elsevier, 2018:51-81.
Thannickal TC, John J, Shan L, et al. Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy. Sci Transl Med 2018;10:eaao4953.
Swaab DF, Bao AM. Matching of the postmortem hypothalamus from patients and controls. Handb. Clin. Neurol. 2021;179:141-156. [cited 2021 Sep 16].
Bossers K, Meerhoff G, Balesar R, et al. Analysis of gene expression in Parkinson's disease: possible involvement of neurotrophic support and axon guidance in dopaminergic cell death. Brain Pathol 2009;19:91-107.
Guo L, Stormmesand J, Fang Z, et al. Quantification of tyrosine hydroxylase and ErbB4 in the locus coeruleus of mood disorder patients using a multispectral method to prevent interference with immunocytochemical signals by neuromelanin. Neurosci. Bull. 2019;35:205-215. [cited 2020 Dec 3].
Shan L, Liu CQ, Balesar R, et al. Neuronal histamine production remains unaltered in Parkinson's disease despite the accumulation of Lewy bodies and Lewy neurites in the tuberomamillary nucleus. Neurobiol Aging 2012;33:1343-1344.
Paxinos G, Huang XF. Atlas of the human brainstem. San Diego: Academic Press, 1995.
Shan L, Bossers K, Unmehopa U, et al. Alterations in the histaminergic system in Alzheimer's disease: a postmortem study. Neurobiol Aging 2012;33:2585-2598.
Fronczek R, Overeem S, Lee SY, et al. Hypocretin (orexin) loss in Parkinson's disease. Brain 2007;130:1577-1585.
Shan L, Bao AM, Swaab DF. The human histaminergic system in neuropsychiatric disorders. Trends Neurosci 2015;38:167-177.
Ericson H, Watanabe T, Kohler C. Morphological analysis of the tuberomammillary nucleus in the rat brain: delineation of subgroups with antibody against L-histidine decarboxylase as a marker5. J Comp Neurol 1987;263:1-24.
Panula P, Airaksinen MS, Pirvola U, Kotilainen E. A histamine-containing neuronal system in human brain. Neuroscience 1990;34:127-132.
Humphries MP, Maxwell P, Salto-Tellez M. QuPath: the global impact of an open source digital pathology system. Comput Struct Biotechnol J 2021;19:852-859. [cited 2022 Jun 6 ].
Gao SF, Qi XR, Zhao J, et al. Decreased NOS1 expression in the anterior cingulate cortex in depression. Cereb. Cortex 2013;23:2956-2964. [cited 2020 Jan 30].
Lu J, Zhao J, Balesar R, et al. Sexually dimorphic changes of hypocretin (orexin) in depression. EBioMedicine 2017;18:311-319.
Shan L, Guo H-Y, van den Heuvel CNAM, et al. Impaired fear extinction in serotonin transporter knockout rats is associated with increased 5-hydroxymethylcytosine in the amygdala. CNS Neurosci Ther 2018;24:810-819.
Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 2005;4:141-194.
Ma XM, Levy A, Lightman SL. Emergence of an isolated arginine vasopressin (AVP) response to stress after repeated restraint: a study of both AVP and corticotropin-releasing hormone messenger ribonucleic acid (RNA) and heteronuclear RNA. Endocrinology 1997;138:4351-4357. [cited 2022 Jul 19].
Takahashi K, Shima T, Soya M, et al. Exercise-induced adrenocorticotropic hormone response is cooperatively regulated by hypothalamic arginine vasopressin and corticotrophin-releasing hormone. Neuroendocrinology 2021;9:894-903. cited 2022 Jul 19.
de Goeij DCE, Kvetnansky R, Whitnall MH, et al. Repeated stress-induced activation of corticotropin-releasing factor neurons enhances vasopressin stores and colocalization with corticotropin-releasing factor in the median eminence of rats. Neuroendocrinology 1991;53:150-159. cited 2022 Jun 2.
de Goeij DCE, Jezova D, Tilders FJH. Repeated stress enhances vasopressin synthesis in corticotropin releasing factor neurons in the paraventricular nucleus. Brain Res 1992;577:165-168. cited 2022 Jun 2.
Erkut ZA, Hofman MA, Ravid R, Swaab DF. Increased activity of hypothalamic corticotropin-releasing hormone neurons in multiple sclerosis. J Neuroimmunol 1995;62:27-33.
Bin LS, Borniger JC, Yamaguchi H, et al. Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression. Sci. Adv. 2020;6:eabc2590 cited 2020 Oct 30.
Ono D, Mukai Y, Hung CJ, et al. The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus. Sci. Adv. 2020;6:eabd0384 cited 2020 Dec 8.
Swaab DF. Brain aging and Alzheimer's disease, “wear and tear” versus “use it or lose it”. Neurobiol Aging 1991;12:317-324.
Shan L, Hofman MA, van Wamelen DJ, et al. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases. Sleep 2012;35:713-715.
Yu X, Zecharia A, Zhang Z, et al. Circadian factor BMAL1 in histaminergic neurons regulates sleep architecture. Curr Biol 2014;24:2838-2844.
McGregor R, Shan L, Wu MF, Siegel JM. Diurnal fluctuation in the number of hypocretin/orexin and histamine producing: implication for understanding and treating neuronal loss. PloS One 2017;12:e0178573.
Brink-Kjaer A, Christensen JAE, Cesari M, et al. Cortical arousal frequency is increased in narcolepsy type 1. Sleep 2021;44:zsaa255. cited 2020 Dec 1.
Maurovich-Horvat E, Keckeis M, Lattová Z, et al. Hypothalamo-pituitary-adrenal axis, glucose metabolism and TNF-α in narcolepsy. J Sleep Res 2014;23:425-431.
Evans R, Kimura H, Alexander R, et al. Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proc. Natl. Acad. Sci. U. S. A. 2022;119:e220753111. [cited 2022 Nov 8].