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dorsal raphe nucleus

Ancy Joseph, Tran Thi Thu Thuy, Le Tat Thanh, Masayoshi Okada
We screened a library of botanical compounds purified from plants of Vietnam for modulators of the activity of a two-pore domain K+ channel, TREK-1, and we identified a hydroxycoumarin-related compound, ostruthin, as an activator of this channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at a low concentration (EC50 = 5.3 μM), and also activity of the TREK-2 channel (EC50 = 3.7 mM). In contrast, ostruthin inhibited other K+ channels, e.g. human ether-à-go-go-related gene (HERG1), inward-rectifier (Kir2...
2018: PloS One
Jessica J Walsh, Daniel J Christoffel, Boris D Heifets, Gabriel A Ben-Dor, Aslihan Selimbeyoglu, Lin W Hung, Karl Deisseroth, Robert C Malenka
Dysfunction in prosocial interactions is a core symptom of autism spectrum disorder. However, the neural mechanisms that underlie sociability are poorly understood, limiting the rational development of therapies to treat social deficits. Here we show in mice that bidirectional modulation of the release of serotonin (5-HT) from dorsal raphe neurons in the nucleus accumbens bidirectionally modifies sociability. In a mouse model of a common genetic cause of autism spectrum disorder-a copy number variation on chromosome 16p11...
August 8, 2018: Nature
Shigeko Takeuchi, Ikuo Tooyama
The TRK-fused gene ( TFG ) is reported to be involved in the regulation of cell size, apoptosis, cell growth, ER-Golgi protein secretion, NF-κβ pathway signaling, the ubiquitin-proteasome system, and pancreatic β-cell mass and function. TFG mutations were reported in some neurodegenerative diseases affecting sensory and motor functions. However, the function of TFG in the nervous system and how TFG mutations lead to neurodegeneration remain unclear. In this study, we employed double immunohistochemistry to investigate the details of TFG localization patterns in monoaminergic and cholinergic neurons in the brainstem...
June 26, 2018: Acta Histochemica et Cytochemica
Christelle Peyron, Claire Rampon, Jean-Marie Petit, Pierre-Hervé Luppi
The dorsal raphe nucleus (DRN) through its extensive efferent projections has been implicated in a great variety of physiological and behavioral functions including the regulation of the sleep-wake cycle. This nucleus is composed of five sub-regions defined according to the distribution of its serotonergic (5-HT) neurons. In addition to its heterogeneity in neuronal populations, the DRN contains a great diversity of 5-HT neuronal subtypes identified based on their electrophysiological characteristics, morphology and sub-regional distribution...
August 2, 2018: Sleep Medicine
Nerea Llamosas, Laura Perez-Caballero, Esther Berrocoso, Cristina Bruzos-Cidon, Luisa Ugedo, Maria Torrecilla
Accumulating evidence indicates that the antidepressant effects of ketamine are, in part, mediated by an increase in the AMPA receptor-mediated neurotransmission in depression related areas, such as the prefrontal cortex (PFC). Therefore, activity in PFC-projecting areas related to major depression, such as the dorsal raphe nucleus (DR), may also be modulated by ketamine. We used whole-cell patch-clamp recordings and western blot experiments to determine whether ketamine promotes acute and maintained alterations in glutamatergic transmission and mTOR pathway in the DR...
July 31, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Natalia L S Machado, Stephen B G Abbott, Jon M Resch, Lin Zhu, Elda Arrigoni, Bradford B Lowell, Patrick M Fuller, Marco A P Fontes, Clifford B Saper
Stress elicits a variety of autonomic responses, including hyperthermia (stress fever) in humans and animals. In this present study, we investigated the circuit basis for thermogenesis and heat conservation during this response. We first demonstrated the glutamatergic identity of the dorsal hypothalamic area (DHAVglut2 ) neurons that innervate the raphe pallidus nucleus (RPa) to regulate core temperature (Tc) and mediate stress-induced hyperthermia. Then, using chemogenetic and optogenetic methods to manipulate this hypothalamomedullary circuit, we found that activation of DHAVglut2 neurons potently drove an increase in Tc, but surprisingly, stress-induced hyperthermia was only reduced by about one-third when they were inhibited...
July 23, 2018: Current Biology: CB
Su-Ying Cui, Jin-Zhi Song, Xiang-Yu Cui, Xiao Hu, Yu-Nu Ma, Yu-Tong Shi, Ying Luo, Yan-Ru Ge, Hui Ding, Hui Ye, Yong-He Zhang
AIM: Sleep disorders are common in Alzheimer's disease (AD) and assumed to directly influence cognitive function and disease progression. This study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular streptozotocin (STZ) administration and assessed the possible underlying mechanisms. METHODS: Cognition ability was assessed in the Morris water maze in rats. Sleep parameters were analyzed by electroencephalographic and electromyographic recordings...
July 16, 2018: CNS Neuroscience & Therapeutics
Hui Zhao, Nur-Ezan Mohamed, Su Jing Chan, Chong Teik Tan, Ran Tao, Victor C Yu, Peter T-H Wong
Modulator of apoptosis 1 (MOAP-1) is a Bcl-2-associated X Protein (BAX)-associating protein that plays an important role in regulating apoptosis. It is highly enriched in the brain but its function in this organ remains unknown. Studies on BAX-/- mice suggested that disruption of programmed cell death may lead to abnormal emotional states. We thus hypothesize that MOAP-1-/- mice may also display stress-related behavioral differences and perhaps involved in stress responses in the brain and investigated if a depression-like trait exists in MOAP-1-/- mice, and if so, whether it is age related, and how it relates to central serotonergic stress response in the dorsal raphe nucleus...
July 12, 2018: Molecular Neurobiology
Reham Shehabeldin, David Lutz, Meliha Karsak, Michael Frotscher, Kerstin Krieglstein, Ahmed Sharaf
Serotonin (5-HT) acts as both a morphogenetic factor during early embryonic development and a neuromodulator of circuit plasticity in the mature brain. Dysregulation of serotonin signaling during critical periods is involved in developmental neurological disorders, such as schizophrenia and autism. In this study we focused on the consequences of defect reelin signaling for the development of the brainstem serotonergic raphe system. We observed that reelin signaling components are expressed by serotonergic neurons during the critical period of their lateral migration...
2018: PloS One
David M Baum, Maud Saussereau, Florine Jeton, Carole Planes, Nicolas Voituron, Philippe Cardot, Marie-Noëlle Fiamma, Laurence Bodineau
We aimed to delineate sex-based differences in neuroplasticity that may be associated with previously reported sex-based differences in physiological alterations caused by repetitive succession of hypoxemia-reoxygenation encountered during obstructive sleep apnea (OSA). We examined long-term changes in the activity of brainstem and diencephalic cardiorespiratory neuronal populations induced by chronic intermittent hypoxia (CIH) in male and female mice by analyzing Fosb expression. Whereas the overall baseline and CIH-induced Fosb expression in females was higher than in males, possibly reflecting different neuroplastic dynamics, in contrast, structures responded to CIH by Fosb upregulation in males only...
2018: Frontiers in Physiology
Lizan Kawa, Alaa Kamnaksh, Joseph B Long, Ulf P Arborelius, Tomas Hökfelt, Denes V Agoston, Mårten Risling
Repeated mild blast-induced traumatic brain injury (rmbTBI), caused by recurrent exposure to low levels of explosive blast, is a significant concern for military health systems. However, the pathobiology of rmbTBI is currently poorly understood. Animal models are important tools to identify the molecular changes of rmbTBI, but comparisons across different models can present their own challenges. In this study, we compared two well-established rodent models of mbTBI, the "KI model" and the "USU/WRAIR model...
2018: Frontiers in Neurology
Yvonne S Davidson, Andrew Robinson, Vee P Prasher, David M A Mann
While post mortem studies have identified the major cell types and functional systems affected in Alzheimer's disease (AD) the initial sites and molecular characteristics of pathology are still unclear. Because individuals with Down syndrome (DS) (trisomy 21) develop the full pathological changes of AD in a predictable way by the time they reach middle to late age, a study of the brains of such persons at different ages makes an ideal 'model system' in which the sites of earliest onset of pathology can be detected and the subsequent progression of changes be monitored...
July 4, 2018: Acta Neuropathologica Communications
Nicolas Giguère, Samuel Burke Nanni, Louis-Eric Trudeau
Significant advances have been made uncovering the factors that render neurons vulnerable in Parkinson's disease (PD). However, the critical pathogenic events leading to cell loss remain poorly understood, complicating the development of disease-modifying interventions. Given that the cardinal motor symptoms and pathology of PD involve the loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc), a majority of the work in the PD field has focused on this specific neuronal population. PD however, is not a disease of DA neurons exclusively: pathology, most notably in the form of Lewy bodies and neurites, has been reported in multiple regions of the central and peripheral nervous system, including for example the locus coeruleus, the dorsal raphe nucleus and the dorsal motor nucleus of the vagus...
2018: Frontiers in Neurology
Neel I Nissen, Kristin R Anderson, Huaixing Wang, Hui Sun Lee, Carly Garrison, Samantha A Eichelberger, Kasarah Ackerman, Wonpil Im, Julie M Miwa
Neuronal nicotinic acetylcholine receptors (nAChRs) of the cholinergic system have been linked to antinociception, and therefore could be an alternative target for pain alleviation. nAChR activity has been shown to be regulated by the nicotinic modulator, lynx1, which forms stable complexes with nAChRs and has a negative allosteric action on their function. The objective in this study was to investigate the contribution of lynx1 to nicotine-mediated antinociception. Lynx1 contribution was investigated by mRNA expression analysis and electrophysiological responses to nicotine in the dorsal raphe nucleus (DRN), a part of the pain signaling pathway...
2018: PloS One
Aya Matsui, Veronica A Alvarez
The ventral pallidum (VP) is part of the basal ganglia circuitry and a target of both direct and indirect pathway projections from the nucleus accumbens. VP is important in cocaine reinforcement, and the firing of VP neurons is modulated in vivo during cocaine self-administration. This modulation of firing is thought to be indirect via cocaine actions on dopamine in the accumbens. Here, we show that cocaine directly inhibits synaptic transmission evoked by selective stimulation of indirect pathway projections to VP neurons...
June 26, 2018: Cell Reports
Juraj Culman, Stephan Mühlenhoff, Annegret Blume, Jürgen Hedderich, Ulf Lützen, Stephen P Hunt, Nadia M J Rupniak, Yi Zhao
Mice lacking the substance P (SP) neurokinin-1 (NK1) receptor (NK1R-/-mice) were used to investigate whether SP affects serotonin (5-HT) function in the brain and to assess the effects of acute immobilisation stress on the hypothalamic-pituitary-adrenocortical (HPA) axis and 5-HT turnover in individual brain nuclei. Basal HPA activity and the expression of hypothalamic corticotropin-releasing hormone (CRH) in wild-type (WT)- and NK1R-/- mice were identical. Stress-induced increases in plasma ACTH concentration were considerably higher in NK1R-/- mice than in WT mice while corticosterone concentrations were equally elevated in both mouse lines...
August 2018: Cellular and Molecular Neurobiology
Jennyfer M Payet, Eliza Burnie, Nick J Sathananthan, Adrian M Russo, Adam J Lawther, Stephen Kent, Christopher A Lowry, Matthew W Hale
Although the neurobiological mechanisms underlying autism spectrum disorder (ASD) are still unknown, dysregulation of serotonergic systems has been implicated in the etiology of ASD, and serotonergic antidepressant drugs are often prescribed to treat some symptoms of ASD. The BALB/c strain of mice express a dysregulated serotonergic system and a phenotype that is relevant to ASD. In this study, juvenile male BALB/c mice were exposed to the selective serotonin reuptake inhibitor fluoxetine either chronically (18 mg/kg/day in drinking water, post-natal day (PND) 28-39) or acutely (18 mg/kg, i...
August 21, 2018: Neuroscience
Júlia Gasull-Camós, Sara Martínez-Torres, Mireia Tarrés-Gatius, Andrés Ozaita, Francesc Artigas, Anna Castañé
Novel fast-acting antidepressant strategies, such as ketamine and deep brain stimulation, enhance glutamatergic neurotransmission in medial prefrontal cortex (mPFC) regions via AMPA receptor (AMPA-R) activation. We recently reported that the regionally-selective blockade of the glial glutamate transporter-1 (GLT-1) by dihydrokainic acid (DHK) microinfusion in rat infralimbic cortex (IL), the most ventral part of the mPFC, evoked immediate (10 min) antidepressant-like responses, which involved AMPA-R activation and were associated to increased serotonin (5-hydroxytryptamine, 5-HT) release...
September 1, 2018: Neuropharmacology
Adrian M Russo, Adam J Lawther, Benjamin M Prior, Luke Isbel, W Gregory Somers, John A Lesku, Amanda L Richdale, Cheryl Dissanayake, Stephen Kent, Christopher A Lowry, Matthew W Hale
Autism spectrum disorder (ASD) is a heterogeneous and highly heritable condition with multiple aetiologies. Although the biological mechanisms underlying ASD are not fully understood, evidence suggests that dysregulation of serotonergic systems play an important role in ASD psychopathology. Preclinical models using mice with altered serotonergic neurotransmission may provide insight into the role of serotonin in behaviours relevant to clinical features of ASD. For example, BALB/c mice carry a loss-of-function single nucleotide polymorphism (SNP; C1473 G) in tryptophan hydroxylase 2 (Tph2), which encodes the brain-specific isoform of the rate-limiting enzyme for serotonin synthesis, and these mice frequently have been used to model symptoms of ASD...
June 20, 2018: Behavioural Brain Research
Shuang Li, Wen-Qing Yao, Ye-Zheng Tao, Lan Ma, Xing Liu
Serotonin (5-hydroxtryptamine, 5-HT), one of the central neurotransmitters, is the most important modulator for emotion regulation, sensory processing, cognitive control, etc. The serotonergic neurons are limited in amount and mainly distributed in the dorsal raphe nucleus (DR) and the median raphe nucleus (MR) in the midline of the brain stem. Previous studies mainly focused on the function of 5-HT neurons in the DR, but little is known about 5-HT neurons in MR. In the present study, with Pet1-Cre transgenic mice and DREADDs technology, we specifically activated or silenced 5-HT neurons in the MR, and aimed to explore their roles in anxiety- and depressive-like behaviors...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
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