Narcolepsy as an Immune-Mediated Disease

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin)-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA) and T cell receptor (TCR) polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development

Vol. 10, Núm. 2 (2012)

La narcolepsia es una enfermedad crónica neurodegenerativa,caracterizada por una regulación anormaldel ciclo vigilia-sueño (CVS), la cual cursa conexcesiva somnolencia diurna (ESD) y manifestacionesanormales del sueño REM (cataplejia, parálisisdel sueño y alucinaciones hipnagógicas y/o hipnopómpicas).Los mecanismos centrales de controldel CVS están alterados en la narcolepsia, teniendouna función crucial en su fisiopatología el hipotálamo,y concretamente el sistema orexinérgico

Narcolepsy and Orexins: An Example of Progress in Sleep Research

Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of orexin-producing neurons in the lateral hypothalamus (LH). It is clinically characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement (REM) sleep such as cataplexy, sleep paralysis and hypnagogic hallucinations. The major pathophysiology of narcolepsy has been recently described on the bases of the discovery of the neuropeptides named orexins (hypocretins) in 1998; considerable evidence, summarized below, demonstrates that narcolepsy is the result of alterations in the genes involved in the pathology of the orexin ligand or its receptor. Deficient orexin transmission is sufficient to produce narcolepsy, as we describe here, animal models with dysregulated orexin signaling exhibit a narcolepsy-like phenotype. Remarkably, these narcoleptic models have different alterations of the orexinergic circuit, this diversity provide us with the means for making comparison, and have a better understanding of orexin cell physiology.It is of particular interest that the most remarkable findings regarding this sleep disorder were fortuitous and due to keen observations. Sleep is a highly intricate and regulated state, and narcolepsy is a disorder that still remains as one of the unsolved mysteries in science. Nevertheless, advances and development of technology in neuroscience will provide us with the necessary tools to unravel the narcolepsy puzzle in the near future.Through an evaluation of the scientific literature we traced an updated picture of narcolepsy and orexins in order to provide insight into the means by which neurobiological knowledge is constructed

Orexin receptor antagonists as therapeutic agents for insomnia

Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor), although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin) neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia

Scientific facts improve cannabis perception and public opinion: results from Sinaloa, México

Abstract Cannabis, the most prevalent drug in Latin America, has long been associated with the state of Sinaloa, Mexico, known for its cultivation and distribution. Despite increasing global acceptance, cannabis use remains stigmatized in Mexican society, driven by perceptions of it as a highly psychoactive and addictive substance lacking medicinal or industrial value. This study investigates the impact of scientific information on societal perceptions of cannabis in Sinaloa. A large convenience sample of 3162 individuals from Sinaloa participated in this research, responding to a questionnaire on cannabis consumption and attitudes. Participants were then subjected to an intervention consisting of an informative briefing based on the documents “Using Evidence to Talk About Cannabis” and “State of the Evidence: cannabis use and regulation" by the International Centre for Science in Drug Policy. After the intervention, participants' attitudes were immediately reevaluated through the same questionnaire, allowing for a comparison of pre- and post-intervention responses. The results indicate that the intervention (providing scientific information) significantly influenced attitudes toward cannabis, with education and age playing prominent roles in its effectiveness. Notably, the intervention fostered more positive or more neutral attitudes, potentially reducing stigma and promoting a better-informed perspective on cannabis. This study highlights the pivotal role of evidence in shaping informed citizens' views, while underscoring the importance of countering misinformation for societal progress. These findings have significant implications for forthcoming cannabis policy modifications in Mexico, emphasizing the necessity of engaging knowledgeable individuals in policy decisions to address the violence and inequalities associated with the illicit drug trade, particularly in Sinaloa