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Teemu Aitta-Aho, Elpiniki Pappa, Denis Burdakov, John Apergis-Schoute
The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration...
October 13, 2016: Neurobiology of Learning and Memory
Amanda C Sharko, Jim R Fadel, Kris F Kaigler, Marlene A Wilson
Identifying the neurobiological mechanisms that underlie differential sensitivity to stress is critical for understanding the development and expression of stress-induced disorders, such as post-traumatic stress disorder (PTSD). Preclinical studies have suggested that rodents display different phenotypes associated with extinction of Pavlovian conditioned fear responses, with some rodent populations being resistant to extinction. An emerging literature also suggests a role for orexins in the consolidation processes associated with fear learning and extinction...
October 13, 2016: Physiology & Behavior
Idan Elbaz, David Zada, Adi Tovin, Tslil Braun, Tali Lerer-Goldshtein, Gordon Wang, Philippe Mourrain, Lior Appelbaum
Sleep is tightly regulated by the circadian clock and homeostatic mechanisms. Although the sleep/wake cycle is known to be associated with structural and physiological synaptic changes that benefit the brain, the function of sleep is still debated. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate various functions including feeding, reward, sleep, and wake. Continuous imaging of single neuronal circuits in live animals is vital to understanding the role of sleep in regulating synaptic dynamics, and the transparency of the zebrafish model enables time-lapse imaging of single synapses during both day and night...
October 12, 2016: Molecular Neurobiology
Aimee Chan, SiHan Li, Ahn R Lee, Joseph Leung, Alissa Yip, Jaimie Bird, Kyle E Godden, Dolores Martinez-Gonzalez, Niels C Rattenborg, Evan Balaban, Maria Pompeiano
Coordinated activity in different sets of widely-projecting neurochemical systems characterize waking (W) and sleep (S). How and when this coordination is achieved during development is not known. We used embryos and newborns of a precocial bird species (chickens) to assess developmental activation in different neurochemical systems using cFos expression, which has been extensively employed to examine cellular activation during S and W in adult mammals. Similarly to adult mammals, newborn awake chicks showed significantly higher cFos expression in W-active hypocretin/orexin (H/O), serotonergic Dorsal Raphe, noradrenergic Locus Coeruleus and cholinergic Laterodorsal and Pedunculopontine Tegmental (Ch-LDT/PT) neurons when compared to sleeping chicks...
October 4, 2016: Neuroscience
Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N Ross, Christopher S Leonard
UNLABELLED: Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xiao-Bing Gao, Tamas L Horvath
A report on the rapid change of activity of hypocretin/orexin cells in response to contact rather than digestion of food delivers new insights into the behavioral control of food intake and systemic energy expenditure.
September 26, 2016: Current Biology: CB
Amir Hossein Emam, Naeimeh Hajesfandiari, Siamak Shahidi, Alireza Komaki, Maziar Ganji, Abdolrahman Sarihi
INTRODUCTION: Recent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats...
September 15, 2016: Brain Research Bulletin
Susumu Tanaka, Yoshiko Honda, Makoto Honda, Hisao Yamada, Kazuki Honda, Tohru Kodama
STUDY OBJECTIVES: Recent findings showed that 16-26% of narcolepsy patients were positive for anti-tribbles pseudokinase 2 (TRIB2) antibody, and the intracerebroventricular administration of IgG purified from anti-TRIB2 positive narcolepsy patients caused hypocretin/orexin neuron loss. We investigated the pathophysiological role of TRIB2 antibody using TRIB2-immunized rats and hypocretin/ataxin-3 transgenic (ataxin-3) mice. METHODS: Plasma, cerebrospinal fluid (CSF), and hypothalamic tissues from TRIB2-immunized rats were collected...
September 9, 2016: Sleep
Régis Lopez, Lucie Barateau, Elisa Evangelista, Sofiene Chenini, Philippe Robert, Isabelle Jaussent, Yves Dauvilliers
STUDY OBJECTIVES: To follow the temporal changes of cerebrospinal fluid biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. METHODS: From 2007 to 2015, 170 HLA DQB1*06:02-positive patients with primary narcolepsy and definite (n=155, 95 males, 36 children) or atypical cataplexy (n=15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively...
September 9, 2016: Sleep
Poul Jørgen Jennum, Lars Østergaard Pedersen, Justyna Maria Czarna Bahl, Signe Modvig, Karina Fog, Anja Holm, Birgitte Rahbek Kornum, Steen Gammeltoft
OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. METHODS: Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases) aged 33 years on average, and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1)...
September 9, 2016: Sleep
Rong-Jian Liu, Catharine Duman, Taro Kato, Brendan Hare, Dora Lopresto, Eunyoung Bang, Jeffery Burgdorf, Joseph Moskal, Jane Taylor, George Aghajanian, Ronald S Duman
GLYX-13 is a putative NMDA receptor modulator with glycine-site partial agonist properties that produces rapid antidepressant effects, but without the psychotomimetic side effects of ketamine. Studies were conducted to examine the molecular, cellular, and behavioral actions of GLYX-13 to further characterize the mechanisms underlying the antidepressant actions of this agent. The results demonstrate that a single dose of GLYX-13 rapidly activates the mTORC1 pathway in the prefrontal cortex (PFC), and that infusion of the selective mTORC1 inhibitor rapamycin into the medial PFC (mPFC) blocks the antidepressant behavioral actions of GLYX-13, indicating a requirement for mTORC1 similar to ketamine...
September 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Camille Planty, Corey P Mallett, Kevin Yim, Jorge C G Blanco, Marina Boukhvalova, Thomas March, Robbert van der Most, Eric Destexhe
An increased risk of narcolepsy following administration of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine (Pandemrix™) was described in children and adolescents in certain European countries. We investigated the potential effects of administration of the AS03-adjuvanted vaccine, non-adjuvanted vaccine antigen and AS03 Adjuvant System alone, on the central nervous system (CNS) in one-month-old cotton rats. Naïve or A(H1N1)pdm09 virus-primed animals received 2 or 3 intramuscular injections, respectively, of test article or saline at two-week intervals...
September 14, 2016: Human Vaccines & Immunotherapeutics
Michel E Mickael, Ashish Rajput, Jannetta Steyn, Lyle Wiemerslage, Thomas Bürglin
The comparative genomics between different rhodopsin-like family groups (α, β, γ and δ) is not well studied. We used a combination of phylogenetic analysis and statistical genomic methods to compare rhodopsin-like family proteins in species likely symbolic of this family's evolutionary progression. For intra-cluster relationships, we applied mathematical optimisation to enhance the tree search produced by the neighbour joining method (NJ) and compared it with maximum likelihood (ML) method. To infer inter-clusters relationships, we used Needleman-Wunsch analysis (NW), HHsearch, ancestral sequence reconstruction and phylogenetic network analysis...
September 3, 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Antonietta Messina, Carolina De Fusco, Vincenzo Monda, Maria Esposito, Fiorenzo Moscatelli, Anna Valenzano, Marco Carotenuto, Emanuela Viggiano, Sergio Chieffi, Vincenzo De Luca, Giuseppe Cibelli, Marcellino Monda, Giovanni Messina
Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation...
2016: Frontiers in Neural Circuits
Zi-Jun Wang, Jian-Feng Liu
Preclinical Research Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non-pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep-wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics...
September 4, 2016: Drug Development Research
Marie Barbier, Christophe Houdayer, Gabrielle Franchi, Fabrice Poncet, Pierre-Yves Risold
The claustrum is a small, elongated nucleus close to the external capsule and deep in the insular cortex. In rodents, this nucleus is characterized by a dense cluster of parvalbumin labeling. The claustrum is connected with the cerebral cortex. It does not project to the brainstem, but brainstem structures can influence this nucleus. To identify some specific projections from the lateral hypothalamus and midbrain, we analyzed the distribution of projections labeled with antibodies against tyrosine hydroxylase (TH), melanin-concentrating hormone (MCH), and hypocretin (Hcrt) in the region of the claustrum...
September 1, 2016: Journal of Comparative Neurology
Huiying Wang, Sa Li, Gilbert J Kirouac
Orexin (hypocretin) neurons located in the posterior hypothalamus send projections to multiple areas of the brain involved in arousal and experimental evidence indicates that these neurons play a role in the physiological and behavioral responses to stress. This study was done to determine if the orexin system was involved in mediating the fear associated with shock context (5×2s of 1.5mA). First, real-time RT-PCR was used to examine changes in the mRNA levels for prepro-orexin (ppOX), the orexin-1 receptor (OX1R) and the orexin-2 receptor (OX2R) at two weeks post-shock...
January 1, 2017: Behavioural Brain Research
Brooke E Schmeichel, Melissa A Herman, Marisa Roberto, George F Koob
BACKGROUND: Cocaine addiction is characterized by patterns of compulsive drug-taking, including preoccupation with obtaining cocaine and loss of control over drug intake. The lateral hypothalamic hypocretin/orexin (HCRT) system has been implicated in drug-taking and the reinstatement of drug-seeking. Evidence suggests that HCRT may drive drug-seeking through activation of specific brain regions implicated in stress system dysfunction, including the central amygdala (CeA). The role of HCRT in the persistence of compulsive-like cocaine-taking has yet to be fully elucidated...
June 16, 2016: Biological Psychiatry
Tomi Sarkanen, Reija Alén, Markku Partinen
INTRODUCTION: Narcolepsy type 1 is an organic sleep disorder caused by the destruction of hypocretin producing neurons in hypothalamus. In addition to daytime sleepiness, the spectrum and severity of symptoms are very variable. Psychiatric comorbidity and phenomena resembling psychotic symptoms are also common. Current treatment options for narcolepsy are symptomatic but there are few case reports of positive effect of immunotherapy. We report a very severely affected young boy treated with rituximab (RXB)...
September 2016: Neurologist
Richard E Rosch, Michael Farquhar, Paul Gringras, Deb K Pal
Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy...
2016: Frontiers in Neurology
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