The Internal Milieu Brain and Body
Rolland S. Parker in Concussive Brain Trauma, 2016
Hypocretins: The hypocretin system and the circadian seem to exchange activation. The hypocretins are two peptides that are synthesized exclusively in the lateral, posterior, and perifornical hypothalamus. They project to such monoaminergic centers as the LC noradrenergic, raphe nucleus (serotonergic), and ventral tegmental (dopaminergic) areas. Hypocretin is an excitatory neuropeptide that activates multiple neuromodulatory systems involved in the regulation of sleep-wake behavior. It activates neuromodulatory cell groups during wakefulness, but less so during slow-wave sleep. Its role during REM sleep is uncertain. While low hypocretin levels have been observed after head trauma, and may result in sleepiness, disturbed capacity to sleep seems more characteristic. Hypocretins may be important in HPA regulation during arousal, and in vagally mediated gastric acid secretion, SNS activation, and cardiovascular function (increased BP and heart rate). This arousal effect may modulate autonomic and sensory functions of the spinal cord, promote energy consumption, produce hyperthermia, and simulate sympathetic tone (Taheri et al., 2006).
Sleep Problems In Children
Michael B O’Neill, Michelle Mary Mcevoy, Alf J Nicholson, Terence Stephenson, Stephanie Ryan in Diagnosing and Treating Common Problems in Paediatrics, 2017
Narcolepsy is a chronic neurological disorder of rapid eye movement sleep characterised by excessive daytime sleepiness, cataplexy (sudden and transient loss of muscle tone often triggered by emotion), hypnogogic or hypnopompic hallucinations (vivid, dreamlike experiences that occur while falling asleep or upon awakening), sleep paralysis and sleep fragmentation. Many symptoms of narcolepsy can occur in patients who are sleep deprived. However, only cataplexy is unique to narcolepsy and indicates that the cause is due to a lack of the hypothalamic neuropeptide hypocretin. Hypocretin is involved in the regulation of the activity of norepinephrine, serotonin, histamine and acetylcholine cell groups. There is a strong association with HLA 0602. There are several reports of an association between the H1N1 2009 vaccine and the development of narcolepsy.
Histamine as Neurotransmitter
Divya Vohora in The Third Histamine Receptor, 2008
Orexin/hypocretin-containing neurons are located in the lateral hypothalamus and perifornical area, close to the histamine neurons, with which they intermingle partially and form a functional entity. Degeneration of hypocretin neurons is the cause of most cases of narcolepsy, with excessive daytime sleepiness and cataplexy [129,130]. Hypocretin neurons maintain wakefulness, particularly in the context of metabolic challenges, and function like a flip-flop switch that prevents frequent transitions among behavioral states [131]. Both hypocretins (1 and 2, also known as orexin A and B) excite histamine neurons through the hypocretin-2 receptor and activation of NCX [94–97]. This action is secondary to a rise in intracellular Ca2+ that probably comes from both extra- and intracellular sources. Hypocretin neurons also express dynorphin that contributes to the excitation of histaminergic neurons by suppressing inhibitory GABAergic inputs [92]. TMN neurons in vivo remain active during cataplexy in narcoleptic hypocretin-2 receptor-deficient dogs [76], and both the effects of hypocretin on vigilance [132] and food intake [133] require H1 receptor (H1R) activation. In contrast to various other knockout (KO) mice, H1R-KO have lower hypocretin levels [134].
An overview of hypocretin based therapy in narcolepsy
Published in Expert Opinion on Investigational Drugs, 2018
Shinichi Takenoshita, Noriaki Sakai, Yuhei Chiba, Mari Matsumura, Mai Yamaguchi, Seiji Nishino
About two decades have passed since the historical discovery of hypocretin/orexin in 1998 by two different research groups. During this period, it has been discovered that this hypothalamic neuropeptide hypocretin plays a pivotal role in the regulation of sleep and wakefulness. At the same time, several studies suggest that narcolepsy with cataplexy is most commonly caused by the loss of hypocretin-producing cells in the hypothalamus (i.e. Narcolepsy Type 1). In previous human studies, low hypocretin-1 level was proved to be a good criterion in Narcolepsy patients. From the ICSD-2 onward, low CSF hypocretin-1 levels have been used to diagnose hypocretin-deficient narcolepsy. Narcolepsy Type 1 is suspected to have strong associations with HLA-DQB1*0602 and with T-cell receptor polymorphisms, which suggests that an autoimmune reaction is the cause for the loss of hypocretin neurons in most Narcolepsy Type 1 patients.
Demographic and Clinical Correlates of Narcolepsy in Adolescents Hospitalized with Mood Disorders: A Nationwide Inpatient Sample (NIS) Study
Published in Behavioral Sleep Medicine, 2023
Rikinkumar S. Patel, Nikhila Veluri, Amit Chopra
Narcolepsy is divided into two types, (i) narcolepsy with cataplexy (NT1) and (ii) narcolepsy without cataplexy (NT2; Plazzi et al., 2018). The term cataplexy can be described as an episode with a brief loss of bilateral muscle tone often triggered by sudden emotions. NT1 is associated with a loss of hypocretin-producing neurons in the dorsolateral hypothalamus, and low cerebrospinal fluid (CSF) hypocretin levels (<110 pg/ml), whereas NT2 is generally associated with normal CSF hypocretin levels. Hypocretin is a neuropeptide that regulates wakefulness and arousal. Additionally, hypocretin has also been associated with appetite regulation, energy metabolism, pain modulation, cardiovascular, and gastrointestinal symptoms (Bassetti et al., 2019).
An evaluation of sodium oxybate as a treatment option for narcolepsy
Published in Expert Opinion on Pharmacotherapy, 2019
The cure for hypocretin neuronal cell loss remains elusive. Available treatments improve symptoms, but narcolepsy patients still struggle to function anywhere close to normal [2]. Various professional societies have published guidelines for therapy [14–16]. In addition to behavioral therapies (napping, exercise, dietary changes, coping, or adaptation methods), a variety of medications have been used to treat narcolepsy. This paper presents an updated review of SXB as a treatment for narcolepsy in adults and children.
Related Knowledge Centers
- Appetite
- Cataplexy
- Lateral Hypothalamus
- Neuropeptide
- Peptide
- Wakefulness
- Arousal
- Narcolepsy
- Orexin-A
- Neuron