Validation of antibodies for neuroanatomical localization of the P2Y11 receptor in macaque brain

Publication date: Available online 8 August 2016 Source:Journal of Chemical Neuroanatomy Author(s): Karin Dreisig, Matilda Degn, Louise Sund, Piotr Hadaczek, Lluis Samaranch, Waldy San Sebastian, Krystof Bankiewicz, Birgitte Rahbek Kornum Focus on the purinergic receptor P2Y11 has increased following the finding of an association between the sleep disorder narcolepsy and a genetic variant in P2RY11 causing decreased gene expression. Narcolepsy is believed to arise from an autoimmune destruction of the hypothalamic neurons that produce the neuropeptide hypocretin/orexin. It is unknown how a decrease in expression of P2Y11 might contribute to an autoimmune reaction towards the hypocretin neurons and the development of narcolepsy. To advance narcolepsy research it is therefore extremely important to determine the neuroanatomical localization of P2Y11 in the brain with particular emphasis on the hypocretin neurons. In this article we used western blot, staining of blood smears, and flow cytometry to select two antibodies for immunohistochemical staining of macaque monkey brain. Staining was seen in neuron-like structures in cortical and hypothalamic regions. Rats do not have a gene orthologue to the P2Y11 receptor and therefore rat brain was used as negative control tissue. The chromogenic signal observed in macaque monkey brain in neurons was not considered reliable, because the antibodies stained rat brain in a similar distribution pattern. Hence, the neuroanatomical localizat...
Source: Journal of Chemical Neuroanatomy - Category: Neuroscience Source Type: research

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AbstractNarcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate). In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medi...
Source: CNS Drugs - Category: Neurology Source Type: research
Narcolepsy is a rare brain disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Stimulants have been used to relieve the symptoms of EDS. Narcolepsy symptoms may pose a risk to burn injury...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Burns, Electricity, Explosions, Fire, Scalds Source Type: news
This article aims to review pitolisant.Areas covered: In this paper the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy and safety of pitolisant was introduced, and the development course of drugs for treating narcolepsy is also briefly described. We performed a systematic review of the literature using PubMed and the following keywords were used: "pitolisant" and "narcolepsy", "cataplexy" and "excessive daytime sleepiness" and "histamine 3 receptor".Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist. It can activat...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Tags: Expert Rev Clin Pharmacol Source Type: research
Abstract Study Objectives: The purpose of this study was to identify patient-centered issues affecting Health-Related Quality of Life (HRQoL) in people with narcolepsy (PWN) and to evaluate patient-reported outcome measures using a mixed-methods approach.Methods: Twenty-nine adults (93% female, mean age = 31 years) with an established diagnosis of narcolepsy (Type I = 58.6%) completed focus group interviews using live videoconferencing. Additionally, participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) measures along with legacy measures commonly used in ...
Source: Behavioral Sleep Medicine - Category: Sleep Medicine Authors: Tags: Behav Sleep Med Source Type: research
Study Objective:We aimed to evaluate the association between patient-reported outcomes (PROs) and treatment regimen/standardized dose (STD), a measure of drug burden, in patients with narcolepsy type 1 (NT1)/type 2 (NT2) and idiopathic hypersomnia (IH).Methods:Patients age 18 years or older with NT1/NT2 and IH with baseline and≥ 6-month follow-up during 2008–2010 were included. Changes in PROs (Epworth Sleepiness Scale [ESS], Fatigue Severity Scale [FSS], Patient Health Questionnaire 9 [PHQ-9], total sleep time [TST]) by diagnosis, treatment regimen (monotherapy versus polytherapy, sodium oxybate [SO] use), and ST...
Source: Journal of Clinical Sleep Medicine : JCSM - Category: Sleep Medicine Source Type: research
CONCLUSIONS: Due to methodological issues, low sample size, and short duration of the clinical trials as well as high risk of bias for outcome reporting, most of the evidence available for this review is of very low or low quality. For results where quality is low or very low, we are uncertain or very uncertain if the effect estimates are true effects, limiting our conclusions. Specifically, we found that modafinil is no better or worse than placebo at preventing worsening of psychosis; however, we are uncertain about this result. We have more confidence that participants receiving modafinil are no more likely to leave a t...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
We report a case of hypersomnia with polysomnographic documentation during the first attack of NMO/SD. Brain MRI revealed bilateral hypothalamic lesions around the third ventricle, whereas optic nerves and spinal cord were intact. The record of the nocturnal video-polysomnography followed by multiple sleep latency tests (MSLT) revealed an abnormal shortened sleep period with a single sleep onset in REM allowing secondary central hypersomnia diagnosis. The recovery of hypersomnia was complete within few months without psychostimulant treatment and the diencephalic lesion disappeared. Thus, diencephalic form of NMO/SD seems ...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
We report a case of hypersomnia with polysomnographic documentation during the first attack of NMO/SD. Brain MRI revealed bilateral hypothalamic lesions around the third ventricle, whereas optic nerves and spinal cord were intact. The record of the nocturnal video-polysomnography followed by multiple sleep latency tests (MSLT) revealed an abnormal shortened sleep period with a single sleep onset in REM allowing secondary central hypersomnia diagnosis. The recovery of hypersomnia was complete within few months without psychostimulant treatment and the diencephalic lesion disappeared. Thus, diencephalic form of NMO/SD seems ...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Introduction: Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor, was effective in treating excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea (OSA) in phase 3 studies.Aims and Objectives: To evaluate long-term safety and efficacy of solriamfetol for EDS in narcolepsy and OSA.Methods: Participants who completed prior solriamfetol studies initiated open-label (OL) solriamfetol with a 2-wk titration followed by a maintenance phase of ≤50 wk. A 2-wk placebo-controlled randomized withdrawal (RW) phase began after 6 mo. Change in Epworth Sleepiness Scale (ESS) during ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Sleep and control of breathing Source Type: research
The dual-acting dopamine and norepinephrine reuptake inhibitor showed durable effects in reducing excessive sleepiness in patients with narcolepsy or obstructive sleep apnea (OSA).International Approvals
Source: Medscape Neurology and Neurosurgery Headlines - Category: Neurology Tags: Neurology & Neurosurgery News Alert Source Type: news
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