Alteration of the striatal dopaminergic system in human narcolepsy

Eisensehr, Ilonka; Linke, Rainer; Tatsch, Klaus; Lindeiner, H v; Kharraz, Bita; Gildehaus, Franz-Josef; Eberle, Rebecca; Pollmächer, Thomas; Schuld, Andreas; Noachtar, Soheyl

doi:10.1212/01.wnl.0000069608.84542.46

Cited by 64 publications

(27 citation statements)

References 9 publications

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“…The volume reduction of gray matter in narcoleptic patients could indicate a disease-related atrophy pattern, although they suggested that these findings require replication in an independent drugnaïve sample of patients. Eisensehr et al [49] assessed the striatal presynaptic dopamine transporter and postsynaptic D2-receptors in seven patients with narcolepsy and seven control subjects using [ 123 I](N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane and [ 123 I](S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyr rolidinyl]methyl)benzamide SPECT. D2-receptor binding was elevated in narcolepsy (P = 0.017) and correlated with the frequency of cataplectic and sleep attacks (r ≥ 0.844; P ≤ 0.017).…”

Section: Narcolepsymentioning

confidence: 99%

Neuroimaging of sleep and sleep disorders

Nofzinger

2006

Curr Neurol Neurosci Rep

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Herein are presented the results of research in the area of sleep neuroimaging over the past year. Significant work has been performed to clarify the basic mechanisms of sleep in humans. New studies also extend prior observations regarding altered brain activation in response to sleep deprivation by adding information regarding vulnerability to sleep deprivation and regarding the influence of task difficulty on aberrant responses. Studies in sleep disorder medicine have yielded significant findings in insomnia, depression, and restless legs syndrome. Extensive advances have been made in the area of sleep apnea where physiologic challenges have been used to probe brain activity in the pathophysiology of sleep apnea syndrome.

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Section: Narcolepsymentioning

confidence: 99%

Neuroimaging of sleep and sleep disorders

Nofzinger

2006

Curr Neurol Neurosci Rep

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“…In the present study, it was not possible to study nocturnal leg movements in more detail. There is evidence that dopamine has a crucial role in PLMS and RLS [41], and changes in the dopamine metabolism in narcolepsy have been observed [42]. It is not known whether these alterations develop simultaneously with the hypocretin deficiency or whether there are some compensatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Polysomnographic and actigraphic characteristics of patients with H1N1-vaccine-related and sporadic narcolepsy

2015

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“…Studies using the canine model of narcolepsy suggest that hypoactivity of dopaminergic and noradrenergic circuits are among the major pathophysiological mechanisms in narcolepsy (38). Recent in vivo brain imaging studies in humans support this notion (9), and the disease is currently treated symptomatically with drugs that enhance monoaminergic (i.e., dopamine, norepinephrine) neurotransmissions (38). In vitro and in vivo studies clearly show that hypocretin peptides stimulate dopaminergic neurons in various brain sites (16,36), which also suggests that hypocretin deficiency may silence dopaminergic circuits.…”

Section: Discussionmentioning

confidence: 99%

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

Kok

Roelfsema

Overeem

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R 2 ϭ 0.46, P ϭ 0.02) and negatively with amount of sleep (R 2 ϭ 0.29, P ϭ 0.048). Patternsynchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P ϭ 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.narcolepsy; thyroid-stimulating hormone; orexin; sleep; entropy NARCOLEPSY IS A NEUROLOGICAL DISORDER, characterized by excessive daytime sleepiness (EDS), hypnagogic hallucinations, cataplexy, and sleep paralysis (41), which affects 20 -60 of every 100,000 subjects in the US and Europe (32). Disruption of hypocretin (orexin) neurotransmission underlies the disease in animals and humans (28,39). Hypocretins (hypocretin-1 and -2, also called orexin A and B) are produced by a small group of neurons in the lateral hypothalamus, which project widely throughout the central nervous system (CNS) (8, 56). The paraventricular nucleus (PVN) is among the various brain sites that receive hypocretin input signals (7). This nucleus harbors neurons that synthesize thyrotropin-releasing hormone (TRH), which is involved in the regulation of the hypothalamo-pituitary-thyroid (HPT) axis (24). During starvation, thyroid hormone secretion is suppressed (2, 52), whereas preprohypocretin mRNA is upregulated in the lateral hypothalamus (4). This led us to hypothesize that hypocretin neural circuits can modulate the activity of hypothalamic TRH neurons and thereby impact the HPT axis.Studies of the puta...

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Alteration of the striatal dopaminergic system in human narcolepsy

Cited by 64 publications

References 9 publications

Neuroimaging of sleep and sleep disorders

Neuroimaging of sleep and sleep disorders

Polysomnographic and actigraphic characteristics of patients with H1N1-vaccine-related and sporadic narcolepsy

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

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