Excitation of Histaminergic Tuberomamillary Neurons by Thyrotropin-Releasing Hormone

Parmentier, Régis; Kolbaev, Sergej; Klyuch, Boris P.; Vandael, David; Lin, Jian‐Sheng; Selbach, Oliver; Haas, Helmut L.; Sergeeva, Olga A.

doi:10.1523/jneurosci.2976-08.2009

Cited by 56 publications

(52 citation statements)

References 57 publications

(76 reference statements)

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“…It is fundamental for appetitive and aversive responses during motivated behavior (24), and blockade of histamine H 1 R in the hypothalamus is believed to be responsible for the weight gain and metabolic dysregulation associated with the clinical use of atypical antipsychotics (25). Several peptides and hormonessuch as leptin, corticotropin-, TSH-releasing hormones, and nefastin-1-are satiety modulators acting, at least in part, through histamine neurons activity (26)(27)(28). So far, there has been no information regarding brain histamine taking part in the anorexic effects of a modulator that, at the dose used in this study, does not easily pass the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

Provensi

Coccurello

Umehara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

108

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Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not known whether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker α-fluoromethylhistidine (α-FMH). α-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H 3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA.histamine receptors | behavioral satiety sequence | BSS | paraventricular hypothalamic nuclei | PVN E ating behavior is regulated by central neurotransmitter systems and peripheral stimuli that interact to change the behavioral state and concur to alter homeostatic aspects of appetite and energy expenditure. The fatty acid amide oleoylethanolamide (OEA) is released by the small intestine in a stimulus-dependent manner and suppresses food intake by activating peroxisome proliferator-activated receptor-α (PPAR-α) (1). Systemic administration of OEA induces c-Fos mRNA expression through the vagus nerve to the nucleus of the solitary tract (NST), supraoptic nuclei (SON), and paraventricular hypothalamic nuclei (PVN) and increases the expression of oxytocin (2, 3), which is involved in the central coordination of homeostatic signals and feeding behavior (4). However, it is not known whether OEA recruits other neurotransmitter systems in the brain to reduce food intake. Histaminergic neurons are clustered in the hypothalamic tuberomammillary nuclei (TMN). They send projections organized in functionally distinct circuits impinging on different brain regions (5), and their firing frequency changes according to the behavioral state (6). Brain histamin...

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Section: Discussionmentioning

confidence: 99%

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

Provensi

Coccurello

Umehara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

108

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“…In the beginning of whole-cell voltage clamp recordings (holding potential −70 mV), TMN neurons were identified by the presence of I A and I H currents (for details see [24]). Inhibitory postsynaptic currents (IPSCs) were evoked by local stimulation through a bipolar stainless-steel stimulating electrode (50 μm; WPI, UK).…”

Section: Methodsmentioning

confidence: 99%

GABAA receptors involved in sleep and anaesthesia: β1- versus β3-containing assemblies

Yanovsky

Schubring

Fleischer

et al. 2011

Pflugers Arch - Eur J Physiol

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The histaminergic neurons of the posterior hypothalamus (tuberomamillary nucleus-TMN) control wakefulness, and their silencing through activation of GABA(A) receptors (GABA(A)R) induces sleep and is thought to mediate sedation under propofol anaesthesia. We have previously shown that the β1 subunit preferring fragrant dioxane derivatives (FDD) are highly potent modulators of GABA(A)R in TMN neurons. In recombinant receptors containing the β3N265M subunit, FDD action is abolished and GABA potency is reduced. Using rat, wild-type and β3N265M mice, FDD and propofol, we explored the relative contributions of β1- and β3-containing GABA(A)R to synaptic transmission from the GABAergic sleep-on ventrolateral preoptic area neurons to TMN. In β3N265M mice, GABA potency remained unchanged in TMN neurons, but it was decreased in cultured posterior hypothalamic neurons with impaired modulation of GABA(A)R by propofol. Spontaneous and evoked GABAergic synaptic currents (IPSC) showed β1-type pharmacology, with the same effects achieved by 3 μM propofol and 10 μM PI24513. Propofol and the FDD PI24513 suppressed neuronal firing in the majority of neurons at 5 and 100 μM, and in all cells at 10 and 250 μM, respectively. FDD given systemically in mice induced sedation but not anaesthesia. Propofol-induced currents were abolished (1-6 μM) or significantly reduced (12 μM) in β3N265M mice, whereas gating and modulation of GABA(A)R by PI24513 as well as modulation by propofol were unchanged. In conclusion, β1-containing (FDD-sensitive) GABA(A)R represent the major receptor pool in TMN neurons responding to GABA, while β3-containing (FDD-insensitive) receptors are gated by low micromolar doses of propofol. Thus, sleep and anaesthesia depend on different GABA(A)R types.

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“…Purkinje neurons (PN) and TMN neurons used for simultaneous recordings of sIPSCs and GABA-evoked currents were isolated in the recording chamber with the help of a vibrodissociation device (14) from slices briefly (5-10 min) pre-incubated with papaine. PNs and TMN neurons were identified by the typical shape and size and with single cell RT PCR by the expression of GAD67 (GABA-synthetizing enzyme) (15) or histidine decarboxylase (HDC, the histamine-producing enzyme) (16,17), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Slices were cryosectioned at 25 m thickness and mounted on gelatin-coated slides and dried before staining, which was performed with the guinea pig polyclonal antibody to HDC (histidine decarboxylase, Acris, Bad Nauheim, Germany) diluted to 1:600 and rabbit anti-GABA A R ␤1-subunit C-terminal (RnDSystems, Wiesbaden-Nordenstadt, Germany, 1:150) according to the protocol published previously (17). Alexa Fluor 488-labeled donkeyanti-rabbit IgG (1:500; Molecular Probes, Eugene, OR) and cy3-labeled goat-anti-guinea pig IgG (1:500; Molecular Probes) were applied to reveal immunoreactivities.…”

Section: Gaba a R Expression Analysis In Native Cells (Single Cell Rtmentioning

confidence: 99%

Fragrant Dioxane Derivatives Identify β1-Subunit-containing GABAA Receptors

Sergeeva

Kletke

Kragler

et al. 2010

Journal of Biological Chemistry

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Nineteen GABA A receptor (GABA A R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of ␤1-subunit-containing GABA A Rs is unknown. Here we report the discovery of a new structural class of GABA A R positive modulators with unique ␤1-subunit selectivity: fragrant dioxane derivatives (FDD). At heterologously expressed ␣1␤x␥2L (x-for 1,2,3) GABA A R FDD were 6 times more potent at ␤1-versus ␤2-and ␤3-containing receptors. Serine at position 265 was essential for the high sensitivity of the ␤1-subunit to FDD and the ␤1N286W mutation nearly abolished modulation; vice versa the mutation ␤3N265S shifted FDD sensitivity toward the ␤1-type. In posterior hypothalamic neurons controlling wakefulness GABA-mediated whole-cell responses and GABAergic synaptic currents were highly sensitive to FDD, in contrast to ␤1-negative cerebellar Purkinje neurons. Immunostaining for the ␤1-subunit and the potency of FDD to modulate GABA responses in cultured hypothalamic neurons was drastically diminished by ␤1-siRNA treatment. In conclusion, with the help of FDDs we reveal a functional expression of ␤1-containing GABA A Rs in the hypothalamus, offering a new tool for studies on the functional diversity of native GABA A Rs. ␥-Aminobutyric acid (GABA),4 the major inhibitory neurotransmitter in the brain, mediates inhibition via GABA A receptors (GABA A R), heteropentameric proteins constructed from subunits derived from several related gene families with six ␣-, three ␤-, three ␥-, one ␦-, one ⑀-, one -, and one -subunit in mammals. In addition 3 rho ()-subunits contribute to what have been called "GABA C receptors" (1). According to the current model of the GABA A R structure the GABA-binding pocket is formed at the ␣/␤-subunit interface, whereas the benzodiazepine (BZ)-binding pocket is located at the ␣/␥ interface (2) with the subunits arranged pseudo-symmetrically around the ion channel in the sequence ␥-␤-␣-␤-␣ anticlockwise when viewed from the synaptic cleft (3).Functional receptor compositions are restricted in their number and delineated on the basis of several criteria such as (i) capability of selected subunits to form a heteropentamer with defined pharmacological properties, (ii) a similar pharmacological fingerprint must be found in native receptors, and (iii) immunohistochemical co-localization of these subunits must be demonstrated at synaptic or extrasynaptic sites (1). Only few subunit combinations are currently accepted as "identified" native GABA A R subtypes with ␤1-containing receptors not among them (1) mainly because subunit-selective pharmacological tools are missing.In total, the GABA A R incorporates more than ten distinct modulatory binding sites targeted by anticonvulsive, antiepileptic, sedative, hypnotic, and anxiolytic compounds belonging to chemically different structural classes (4 -7) with some of them showing receptor type-specific actions. Benzodiazepine (BZ)-site agonists discriminate ␥2-containing GABA A Rs from recombi...

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Excitation of Histaminergic Tuberomamillary Neurons by Thyrotropin-Releasing Hormone

Cited by 56 publications

References 57 publications

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

GABAA receptors involved in sleep and anaesthesia: β1- versus β3-containing assemblies

Fragrant Dioxane Derivatives Identify β1-Subunit-containing GABAA Receptors

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