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tuberomammillary nucleus

Jun-Fan Xie, Kun Fan, Can Wang, Peng Xie, Min Hou, Le Xin, Guang-Fu Cui, Lin-Xin Wang, Yu-Feng Shao, Yi-Ping Hou
A prominent hypothesis, the "flip-flop switch" model, predicts that histaminergic (HAergic) neurons in the tuberomammillary nucleus (TMN), an important component of the ascending arousal system, are inactivated by GABA mainly from the ventrolateral preoptic nucleus to allow the appearance and maintenance of sleep. However, which sleep state and the band of EEG activity induced by GABAergic inactivation of the TMN are unclear. In this study, alterations of sleep-wake states and cortical EEG power spectral density were investigated following muscimol, a GABAA-receptor agonist, microinjected bilaterally into the TMN in freely moving rats and HA pretreated rats, respectively...
April 1, 2017: Neurochemical Research
Meng-Qi Zhang, Tian-Xiao Wang, Rui Li, Zhi-Li Huang, Wu-Jian Han, Xiao-Chang Dai, Yi-Qun Wang
Natural helicid (4-formylphenyl-O-β-d-allopyranoside), a main active constituent from seeds of the Chinese herb Helicia nilagirica, has been reported to exert a sedative, analgesic and hypnotic effect, and is used clinically to treat neurasthenic syndrome, vascular headaches and trigeminal neuralgia. In the current study, mechanical allodynia tests, electroencephalograms, electromyogram recordings and c-Fos expression in neuropathic pain-like model mice of partial sciatic nerve ligation were used to investigate the effect of helicid on neuropathic pain and co-morbid insomnia...
March 20, 2017: Journal of Sleep Research
Ko Yamanaka, Sabine S Gouraud, Miwa Takagishi, Akira Kohsaka, Masanobu Maeda, Hidefumi Waki
The tuberomammillary nucleus (TMN) of the posterior hypothalamus has a high density of histaminergic neurons, the projection fibers of which are present in many areas of the brain, including the nucleus tractus solitarius (NTS), which controls arterial pressure (AP). In this study, we investigated whether the TMN-NTS pathway is involved in central cardiovascular regulation. Bicuculline, a gamma-aminobutyric acid type A (GABAA) receptor antagonist, was microinjected into the ventral TMN of anesthetized rats and its effects on AP and heart rate (HR) were observed...
March 2017: Physiological Reports
A Diez-Garcia, M Garzon
Distributed neural networks in the brain sustain generation of wakefulness and two sleep states: non-REM sleep and REM sleep. These three behavioral states are jointly ingrained in a rhythmic sequence that constitutes the sleep-wakefulness cycle. This paper reviews and updates knowledge about the involvement of the histaminergic system in sleep-wakefulness cycle organization. Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, but are the source of a widespread projection system to many brain regions...
March 16, 2017: Revista de Neurologia
Jerrah Holth, Tirth Patel, David M Holtzman
Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep wake cycle and is higher during wakefulness and lower during sleep...
January 2017: Neurobiology of Sleep and Circadian Rhythms
Nicholas I Cilz, Saobo Lei
In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception, and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H1 , H2 , and H3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC50 of 1...
May 2017: Hippocampus
Gloria E Hoffman, Michael Koban
A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC), would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD) because histamine plays a major role in maintaining wakefulness...
2016: PloS One
Ramsés Jiménez-Moreno, Adrián Amaury Farret-Ramos, Adriana Valle-Ayala, Niurka Trujillo-Paredes, Eric Murillo-Rodríguez
BACKGROUND: Modafinil (MOD) is a waking-promoting compound that is used for treatment of sleep disorders such as sleepiness and narcolepsy. Despite its efficiency, there are missing pieces of evidence regarding the mechanism of action of MOD at molecular level. For example, current data have demonstrated that MOD induces alertness by activating several wake-related neurotransmitter receptors, including dopamine 1 (D1) receptor. Nevertheless, an intriguing point highlights that MOD might be activating intracellular elements bounded to D1 receptor, such as cAMP response element-binding (CREB) or mitogen-activated protein kinase (MAP-K) expression...
December 14, 2016: Current Molecular Pharmacology
Eun Y Lee, Young G Hwang, Hyun S Lee
Based on the importance of tuberomammillary nucleus (TMN) as a target for feeding/arousal-related functions, we aimed in the present study to investigate hypothalamic neuronal origin of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) fibers projecting to the histaminergic nucleus. In the first series of experiments, we examined NPY (or CART) fiber distribution within the boundary of adenosine deaminase (ADA)-immunoreactive (ir) TMN regions; extensive NPY (or CART)-ir axon terminals were observed in E4 (TMMd), E3 (TMMv), and E2 (TMVr) subdivisions...
December 3, 2016: Brain Research
Rachel A Cliburn, Amy R Dunn, Kristen A Stout, Carlie A Hoffman, Kelly M Lohr, Alison I Bernstein, Emily J Winokur, James Burkett, Yvonne Schmitz, William M Caudle, Gary W Miller
Vesicular monoamine transporter 2 (VMAT2, SLC18A2) is a transmembrane transporter protein that packages dopamine, serotonin, norepinephrine, and histamine into vesicles in preparation for neurotransmitter release from the presynaptic neuron. VMAT2 function and related vesicle dynamics have been linked to susceptibility to oxidative stress, exogenous toxicants, and Parkinson's disease. To address a recent depletion of commonly used antibodies to VMAT2, we generated and characterized a novel rabbit polyclonal antibody generated against a 19 amino acid epitope corresponding to an antigenic sequence within the C-terminal tail of mouse VMAT2...
November 9, 2016: Journal of Chemical Neuroanatomy
David S Uygun, Zhiwen Ye, Anna Y Zecharia, Edward C Harding, Xiao Yu, Raquel Yustos, Alexei L Vyssotski, Stephen G Brickley, Nicholas P Franks, William Wisden
Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kento Ujita, Ken-Ichi Kinoshita, Yoshikage Muroi, Toshiaki Ishii
AIMS: Bilateral lesions of the mesencephalic trigeminal sensory nucleus (Me5), which receives histaminergic neurons from the tuberomammillary nucleus (TMN), alter nocturnal feeding and related behaviors in mice, concomitant with a decrease in orexin mRNA level in the perifornical area (PFA) during the dark phase. Therefore, we investigated the neuronal input to the TMN from the Me5, as well as the effects of TMN lesions on the circadian profiles of feeding and related behaviors. MAIN METHODS: We examined the presence of neurons projecting from the Me5 to the TMN by direct injection of a retrograde tracer, Fluorogold, into the TMN E2 sub-region (TMN-E2)...
October 1, 2016: Life Sciences
Yu Sun, Shi-Yu Jiang, Jian Ni, Yan-Jia Luo, Chang-Rui Chen, Zong-Yuan Hong, Yuchio Yanagawa, Wei-Min Qu, Lu Wang, Zhi-Li Huang
AIM: Ethanol, one of the most frequently used and abused substances in our society, has a profound impact on sedation. However, the neuronal mechanisms underlying its sedative effect remain unclear. In this study, we investigated the effects of ethanol on histaminergic neurons in the tuberomammillary nucleus (TMN), a brain region thought to be critical for wakefulness. METHODS: Coronal brain slices (250 μm thick) containing the TMN were prepared from GAD67-GFP knock-in mice...
September 2016: Acta Pharmacologica Sinica
Gabriela Flores-Balter, Héctor Cordova-Jadue, Alessandra Chiti-Morales, Carolyne Lespay, Pablo Espina-Marchant, Romina Falcon, Noemi Grinspun, Jessica Sanchez, Diego Bustamante, Paola Morales, Mario Herrera-Marschitz, José L Valdés
Perinatal asphyxia (PA) is associated with long-term neuronal damage and cognitive deficits in adulthood, such as learning and memory disabilities. After PA, specific brain regions are compromised, including neocortex, hippocampus, basal ganglia, and ascending neuromodulatory pathways, such as dopamine system, explaining some of the cognitive disabilities. We hypothesize that other neuromodulatory systems, such as histamine system from the tuberomammillary nucleus (TMN), which widely project to telencephalon, shown to be relevant for learning and memory, may be compromised by PA...
October 15, 2016: Behavioural Brain Research
Anne Venner, Christelle Anaclet, Rebecca Y Broadhurst, Clifford B Saper, Patrick M Fuller
The largest synaptic input to the sleep-promoting ventrolateral preoptic area (VLPO) [1] arises from the lateral hypothalamus [2], a brain area associated with arousal [3-5]. However, the neurochemical identity of the majority of these VLPO-projecting neurons within the lateral hypothalamus (LH), as well as their function in the arousal network, remains unknown. Herein we describe a population of VLPO-projecting neurons in the LH that express the vesicular GABA transporter (VGAT; a marker for GABA-releasing neurons)...
August 22, 2016: Current Biology: CB
Ana Maricela García-Gálvez, José Antonio Arias-Montaño
Histamine plays a significant role as a neuromodulator in the human central nervous system. Histamine-releasing neurons are exclusively located in the tuberomammillary nucleus of the hypothalamus, project to all major areas of the brain, and participate in functions such as the regulation of sleep/wakefulness, locomotor activity, feeding and drinking, analgesia, learning, and memory. The functional effects of histamine are exerted through the activation of four G protein-coupled receptors (H1, H2, H3 and H4), and in the central nervous system the first three receptors are widely expressed...
January 2016: Gaceta Médica de México
Chang-Rui Chen, Yu Sun, Yan-Jia Luo, Xin Zhao, Jiang-Fan Chen, Yuchio Yanagawa, Wei-Min Qu, Zhi-Li Huang
Paeoniflorin (PF, C23H28O11), one of the principal active ingredients of Paeonia Radix, exerts depressant effects on the central nervous system. We determined whether PF could modulate sleep behaviors and the mechanisms involved. Electroencephalogram and electromyogram recordings in mice showed that intraperitoneal PF administered at a dose of 25 or 50 mg/kg significantly shortened the sleep latency and increased the amount of non-rapid eye movement (NREM). Immunohistochemical study revealed that PF decreased c-fos expression in the histaminergic tuberomammillary nucleus (TMN)...
January 2016: Journal of Pharmacology and Experimental Therapeutics
Mark A Babizhayev
INTRODUCTION: Diabetes mellitus is the seventh-leading cause of death in the US and diabetic complications are interlaced with specific diverse microvascular and macrovascular pathologies resulting from hyperglycemia. The society should expand prowess and patenting of biotechnology to cure disease and complications. AREAS COVERED: The work summarizes biological activities of patented carnosine mimetics resistant in formulations to enzymatic hydrolysis with human carnosinases that are acting as a universal form of antioxidant, deglycating and transglycating agents that inhibit sugar-mediated protein crosslinking, chelate or inactivate a number of transition metal ions (including ferrous and copper ions), possess lipid peroxidase type of activity and protection of antioxidant enzymes from inactivation...
2015: Expert Opinion on Therapeutic Patents
Eduardo E Benarroch, Ann M Schmeichel, Joseph E Parisi, Phillip A Low
BACKGROUND: Histaminergic neurons of the tuberomammillary nucleus are critical for maintenance of wakefulness and participate in basal ganglia modulation and sympathoexcitation. All of these functions are affected in multiple system atrophy and dementia with Lewy bodies. OBJECTIVES: To determine the involvement of histaminergic neurons in these synucleinopathies. METHODS: Immunocytochemical staining for histidine decarboxylase and stereological cell counts in the posterolateral hypothalamus from six cases with multiple system atrophy, six with dementia with Lewy bodies, and five healthy controls...
July 2015: Movement Disorders: Official Journal of the Movement Disorder Society
Mark A Babizhayev, Yegor E Yegorov
BACKGROUND: Visual impairment broadly impacts the ability of affected people to maintain their function and to remain independent during their daily occupations as they grow older. Visual impairment affects survival of older patients, quality of life, can affect a person's self-ranking of health, may be associated with social and functional decline, use of community support services, depression, falls, nursing home placement, and increased mortality. It has been hypothesized that senile cataract may serve as a marker for generalised tissue aging, since structural changes occurring in the proteins of the lens during cataract formation are similar to those which occur elsewhere as part of the aging process...
2016: Recent Patents on Drug Delivery & Formulation
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