Reduced Numbers of Corticotropin‐Releasing Hormone Neurons in Narcolepsy Type 1

Shan, Ling; Balesar, Rawien; Swaab, Dick F.; Lammers, Gert Jan; Fronczek, Rolf

doi:10.1002/ana.26300

Cited by 18 publications

(19 citation statements)

References 20 publications

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“…However, strong behavioral arousal is required in stressful situations, and PVH CRH neurons actively mediate stress-induced insomnia via the PVH CRH →LHHcrt pathway [8]. The above studies provide evidence to support the role for the PVH in controlling sleep–wake states from three aspects, as suggested from human clinical observations [29, 30] and animal experiments.…”

Section: Discussionmentioning

confidence: 81%

“…1(c)] [29], indicating disrupted sleep structures following lesions. Another clinical observation reported that there was a substantial loss (97%) of hypocretin-1 immunoreactive and CRH neurons (88%) in the PVH, along with markedly less CRH-positive fibers in the ME, in narcolepsy type 1 postmortem brains [30]. In contrast, other major neuronal types (AVP, orexin/hypocretin, tyrosine hydroxylase, and TRH) in the PVH were unaffected [30].…”

Section: Lesion Studiesmentioning

confidence: 99%

“…Another clinical observation reported that there was a substantial loss (97%) of hypocretin-1 immunoreactive and CRH neurons (88%) in the PVH, along with markedly less CRH-positive fibers in the ME, in narcolepsy type 1 postmortem brains [30]. In contrast, other major neuronal types (AVP, orexin/hypocretin, tyrosine hydroxylase, and TRH) in the PVH were unaffected [30]. These two clinical reports and animal experiments all imply that dysfunction of the PVH leads to an overabundance of sleep and provides solid evidence of the necessity of PVH neurons in physiological arousal.…”

Section: Lesion Studiesmentioning

confidence: 99%

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Role of the paraventricular nucleus of the hypothalamus in sleep–wake regulation

Jiang

Chen

Huang

et al. 2022

Brain Science Advances

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The paraventricular nucleus of the hypothalamus (PVH) acts as a cohesive functional unit that regulates neuroendocrine and autonomic function, complex behavior, and negative emotions after stress. However, how the PVH integrates arousal with these biological functions has only recently been explored. Clinical reports, combined with neurotoxic lesioning, immunochemistry, neuronal activity recordings, and the polysomnographic analyses of genetically modified animals, have revealed that the PVH is important for the control of wakefulness. Here, we review emerging anatomical and neural mechanisms for sleep–wake regulation in the PVH to support its essential role in the promotion and maintenance of wakefulness.

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Section: Discussionmentioning

confidence: 81%

Section: Lesion Studiesmentioning

confidence: 99%

Section: Lesion Studiesmentioning

confidence: 99%

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Role of the paraventricular nucleus of the hypothalamus in sleep–wake regulation

Jiang

Chen

Huang

et al. 2022

Brain Science Advances

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“…Patients with PD, AD, Kleine-Levin Syndrome, and idiopathic hypersomnia, in which LH orexinergic and PB glutamatergic neurons are thought to function normally, still show hypersomnolence ( Bollu et al, 2018 ). Furthermore, dysfunctions of the PVH induced hypersomnia-like behaviors in mice ( Chen et al, 2021 ) and patients with narcolepsy type 1 showed reduced numbers of corticotropin-releasing hormone neurons in the PVH ( Shan et al, 2022 ), further supporting the importance of the PVH in arousal controlling and maintenance. Therefore, our case report first provides clinical evidence that dysfunctions of the PVH area led to hypersomnia in patients.…”

Section: Discussionmentioning

confidence: 96%

“…Besides, some studies reported the association between AQP4-IgG, MOG antibodies and hypersomnia ( Kaur et al, 2013 ; Bollu et al, 2018 ; Chen et al, 2021 ) or disorder associated with MOG antibodies and hypersomnia ( Liu et al, 2020 ), with regression of hypersomnia after appropriate treatment of the autoimmune disease. On the other hand, it has been recently shown that an up-regulation of anti-MOG antibodies can be modulated by prolactin ( Shan et al, 2022 ), a hormone correlated with the onset of hypersomnia ( Kume et al, 2015 ). These findings indicated the potential role of the inflammatory/autoimmune pathogenesis underlying hypersomnia in these three cases with lesions of PVH area.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Dysfunction of the Paraventricular Hypothalamic Nucleus Area Induces Hypersomnia in Patients

et al. 2022

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BackgroundHypersomnia is a common and highly impairing symptom marked by pathological excessive sleepiness, which induces suboptimal functioning and poor quality of life. Hypersomnia can be both a primary (e.g., hypersomnolence disorder) and secondary (e.g., tumors, and head trauma) symptom of disorders. However, its underlying mechanisms remain largely unknown.Case PresentationWe report that three clinical cases with lesions around the paraventricular nucleus of the hypothalamus (PVH) area showed excessive daytime sleepiness and a prolonged nocturnal sleep lasting more than 20 h per day. Sleep architecture and subjective daytime sleepiness were examined by polysomnography. These cases were presented with stroke, myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders and neuromyelitis optical spectrum disorder (NMOSD), respectively. Magnetic resonance imaging (MRI) showed lesions around the PVH area in all these three patients. After treatment of their primary disorders, their excessive sleep decreased as the PVH area recovered.ConclusionOur findings suggest that the PVH may play an essential role in the occurrence of hypersomnia.

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Activated Wake Systems in Narcolepsy Type 1

Shan,

Linssen,

Harteman

et al. 2023

Annals of Neurology

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ObjectiveNarcolepsy 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.MethodsIn 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).ResultsIn 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.InterpretationOur 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

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Reduced Numbers of Corticotropin‐Releasing Hormone Neurons in Narcolepsy Type 1

Cited by 18 publications

References 20 publications

Role of the paraventricular nucleus of the hypothalamus in sleep–wake regulation

Role of the paraventricular nucleus of the hypothalamus in sleep–wake regulation

Case Report: Dysfunction of the Paraventricular Hypothalamic Nucleus Area Induces Hypersomnia in Patients

Activated Wake Systems in Narcolepsy Type 1

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