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Astrocyte glutamate neuron dopamine

Ahmad Seif Kanaan, Sarah Gerasch, Isabel García-García, Leonie Lampe, André Pampel, Alfred Anwander, Jamie Near, Harald E Möller, Kirsten Müller-Vahl
Gilles de la Tourette syndrome is a hereditary, neuropsychiatric movement disorder with reported abnormalities in the neurotransmission of dopamine and γ-aminobutyric acid (GABA). Spatially focalized alterations in excitatory, inhibitory and modulatory neurochemical ratios within specific functional subdivisions of the basal ganglia, may lead to the expression of diverse motor and non-motor features as manifested in Gilles de la Tourette syndrome. Current treatment strategies are often unsatisfactory thus provoking the need for further elucidation of the underlying pathophysiology...
January 2017: Brain: a Journal of Neurology
Sonu Singh, Akanksha Mishra, Neha Srivastava, Rakesh Shukla, Shubha Shukla
Parkinson's disease is accompanied by nonmotor symptoms including cognitive impairment, which precede the onset of motor symptoms in patients and are regulated by dopamine (DA) receptors and the mesocorticolimbic pathway. The relative contribution of DA receptors and astrocytic glutamate transporter (GLT-1) in cognitive functions is largely unexplored. Similarly, whether microglia-derived increased immune response affects cognitive functions and neuronal survival is not yet understood. We have investigated the effect of acetyl-L-carnitine (ALCAR) on cognitive functions and its possible underlying mechanism of action in 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats...
December 14, 2016: Molecular Neurobiology
Qiaoling Cui, Jason E Pitt, Arin Pamukcu, Jean-Francois Poulin, Omar S Mabrouk, Michael P Fiske, Isabel B Fan, Elizabeth C Augustine, Katherine A Young, Robert T Kennedy, Rajeshwar Awatramani, C Savio Chan
The prevailing circuit model predicts that hyperactivity of the striatopallidal pathway and subsequently increased inhibition of external globus pallidus (GPe) neurons lead to the hypokinetic symptoms of Parkinson's disease (PD). It is believed that hyperactivity of the striatopallidal pathway is due to inactivity of dopamine receptors on the somatodendritic membrane of striatopallidal neurons, but the exact cellular underpinnings remain unclear. In this study, we show that mouse GPe astrocytes critically control ambient glutamate level, which in turn gates striatopallidal transmission via the activation of presynaptic metabotropic glutamate receptors...
November 22, 2016: Cell Reports
Mika Takeshima, Ikuko Miyazaki, Shinki Murakami, Taizo Kita, Masato Asanuma
l-Theanine (γ-glutamylethylamide), a component of green tea, is considered to have regulatory and neuroprotective roles in the brain. The present study was designed to determine the effect of l-theanine on excess dopamine-induced neurotoxicity in both cell culture and animal experiments. The primary cultured mesencephalic neurons or co-cultures of mesencephalic neurons and striatal astrocytes were pretreated with l-theanine for 72 h, and then treated with excess dopamine for further 24 h. The cell viability of dopamine neurons and levels of glutathione were evaluated...
September 2016: Journal of Clinical Biochemistry and Nutrition
L Hondebrink, A H A Verboven, W S Drega, S Schmeink, M W G D M de Groot, R G D M van Kleef, F M J Wijnolts, A de Groot, J Meulenbelt, R H S Westerink
Annual prevalence of the use of common illicit drugs and new psychoactive substances (NPS) is high, despite the often limited knowledge on the health risks of these substances. Recently, cortical cultures grown on multi-well microelectrode arrays (mwMEAs) have been used for neurotoxicity screening of chemicals, pharmaceuticals, and toxins with a high sensitivity and specificity. However, the use of mwMEAs to investigate the effects of illicit drugs on neuronal activity is largely unexplored. We therefore first characterised the cortical cultures using immunocytochemistry and show the presence of astrocytes, glutamatergic and GABAergic neurons...
July 2016: Neurotoxicology
Jennifer R Ayers-Ringler, Yun-Fang Jia, Yan-Yan Qiu, Doo-Sup Choi
Alcohol use disorder (AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol (measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors...
March 22, 2016: World Journal of Psychiatry
Paul Castellano, Chisom Nwagbo, Luis R Martinez, Eliseo A Eugenin
Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine...
May 2016: Journal of Neurochemistry
Ikuko Miyazaki, Shinki Murakami, Nao Torigoe, Yoshihisa Kitamura, Masato Asanuma
Astrocytes but not neurons express cystine/glutamate exchange transporter (xCT), which takes up cystine, and consequently supplies the substrate for GSH synthesis in neurons. It is recognized that GSH synthesis in neurons is dependent on the expression of xCT in astrocytes. Previous studies reported that levetiracetam (LEV), an anti-epileptic drug, increased xCT expression in vivo. The purpose of this study was to examine neuroprotective effects of LEV in parkinsonian models and demonstrate xCT in astrocytes as a target of neuroprotection against dopaminergic neurodegeneration...
January 2016: Journal of Neurochemistry
J Andrew Hardaway, Sarah M Sturgeon, Chelsea L Snarrenberg, Zhaoyu Li, X Z Shawn Xu, Daniel P Bermingham, Peace Odiase, W Clay Spencer, David M Miller, Lucia Carvelli, Shannon L Hardie, Randy D Blakely
Glial cells play a critical role in shaping neuronal development, structure, and function. In a screen for Caenorhabditis elegans mutants that display dopamine (DA)-dependent, Swimming-Induced Paralysis (Swip), we identified a novel gene, swip-10, the expression of which in glia is required to support normal swimming behavior. swip-10 mutants display reduced locomotion rates on plates, consistent with our findings of elevated rates of presynaptic DA vesicle fusion using fluorescence recovery after photobleaching...
June 24, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Chun-Ling Duan, Chong-Wei Liu, Shu-Wen Shen, Zhang Yu, Jia-Lin Mo, Xian-Hua Chen, Feng-Yan Sun
To determine whether reactive astrocytes stimulated by brain injury can transdifferentiate into functional new neurons, we labeled these cells by injecting a glial fibrillary acidic protein (GFAP) targeted enhanced green fluorescence protein plasmid (pGfa2-eGFP plasmid) into the striatum of adult rats immediately following a transient middle cerebral artery occlusion (MCAO) and performed immunolabeling with specific neuronal markers to trace the neural fates of eGFP-expressing (GFP(+)) reactive astrocytes. The results showed that a portion of striatal GFP(+) astrocytes could transdifferentiate into immature neurons at 1 week after MCAO and mature neurons at 2 weeks as determined by double staining GFP-expressing cells with βIII-tubulin (GFP(+)-Tuj-1(+)) and microtubule associated protein-2 (GFP(+)-MAP-2(+)), respectively...
September 2015: Glia
Andiara E Freitas, Javier Egea, Izaskun Buendia, Vanessa Gómez-Rangel, Esther Parada, Elisa Navarro, Ana Isabel Casas, Aneta Wojnicz, José Avendaño Ortiz, Antonio Cuadrado, Ana Ruiz-Nuño, Ana Lúcia S Rodrigues, Manuela G Lopez
Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension of this previous study by assessing the antidepressant-like effect of agmatine in an animal model of depression induced by corticosterone in mice. Swiss mice were treated simultaneously with agmatine or imipramine at a dose of 0...
July 2016: Molecular Neurobiology
Marco Matos, Hai-Ying Shen, Elisabete Augusto, Yumei Wang, Catherine J Wei, Yu Tian Wang, Paula Agostinho, Detlev Boison, Rodrigo A Cunha, Jiang-Fan Chen
BACKGROUND: Adenosine A2A receptors (A2AR) modulate dopamine and glutamate signaling and thereby may influence some of the psychomotor and cognitive processes associated with schizophrenia. Because astroglial A2AR regulate the availability of glutamate, we hypothesized that they might play an unprecedented role in some of the processes leading to the development of schizophrenia, which we investigated using a mouse line with a selective deletion of A2AR in astrocytes (Gfa2-A2AR knockout [KO] mice]...
December 1, 2015: Biological Psychiatry
Aisa N Chepkova, Susanne Schönfeld, Olga A Sergeeva
Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old) to old (18-24 months of age) animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO) synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor) was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers...
2015: Neural Plasticity
Anthony Bosson, Sylvie Boisseau, Alain Buisson, Marc Savasta, Mireille Albrieux
The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia circuitry particularly sensitive to pathological dopamine depletion. Indeed, hyperactivity of SNr neurons is known to be responsible for some motor disorders characteristic of Parkinson's disease. The neuronal processing of basal ganglia dysfunction is well understood but, paradoxically, the role of astrocytes in the regulation of SNr activity has rarely been considered. We thus investigated the influence of the disruption of dopaminergic transmission on plastic changes at tripartite glutamatergic synapses in the rat SNr and on astrocyte calcium activity...
April 2015: Glia
Daniel Simão, Catarina Pinto, Stefania Piersanti, Anne Weston, Christopher J Peddie, André E P Bastos, Valerio Licursi, Sigrid C Schwarz, Lucy M Collinson, Sara Salinas, Margarida Serra, Ana P Teixeira, Isabella Saggio, Pedro A Lima, Eric J Kremer, Giampietro Schiavo, Catarina Brito, Paula M Alves
Advances in mechanistic knowledge of human neurological disorders have been hindered by the lack of adequate human in vitro models. Three-dimensional (3D) cellular models displaying higher biological relevance are gaining momentum; however, their lack of robustness and scarcity of analytical tools adapted to three dimensions hampers their widespread implementation. Herein we show that human midbrain-derived neural progenitor cells, cultured as 3D neurospheres in stirred culture systems, reproducibly differentiate into complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes...
February 2015: Tissue Engineering. Part A
Travis Rush, Alain Buisson
It is becoming increasingly clear that aberrant neuronal activity can be the cause and the result of amyloid beta production. Synaptic activation facilitates non-amyloidogenic processing of amyloid precursor protein (APP) and cell survival, primarily through synaptic NMDA receptors (NMDARs) and perhaps specifically those containing GluN2A-subunits. In contrast, extrasynaptic and GluN2B-containing NMDARs promote beta-secretase cleavage of APP into amyloid-beta (Aβ). The opposing nature of these NMDAR populations is reflected in their control over cell survival and death pathways...
May 2014: Cell and Tissue Research
Takashi Suto, Amie L Severino, James C Eisenach, Ken-ichiro Hayashida
Gabapentin has shown to be effective in animals and humans with acute postoperative and chronic pain. Yet the mechanisms by which gabapentin reduces pain have not been fully addressed. The current study performed in vivo microdialysis in the locus coeruleus (LC) in normal and spinal nerve ligated (SNL) rats to examine the effect of gabapentin on extracellular glutamate concentration and its mechanisms of action with focus on presynaptic GABA-B receptors, astroglial glutamate transporter-1 (GLT-1), and interactions with α2δ subunits of voltage-gated Ca(2+) channels and endogenous noradrenaline...
June 2014: Neuropharmacology
Ute Krügel, László Köles, Péter Illés
The medial prefrontal cortex (PFC) is thought to be the highest order association area in the mammalian cortex which is involved in cognitive functions. Especially, layer V pyramidal cells integrating afferent innervations from dopaminergic cell groups in the ventral tegmental area, glutamatergic inputs from the thalamus and neighbouring PFC pyramical cells, as well as GABAergic inputs from local interneurons are crucial for processing short-term working memory. These neurons are endowed with the NMDA- and AMPA-type excitatory amino acid receptors, described to be involved in the regulation of synaptic plasticity, the apparent basis of elementary learning processes...
December 2013: Neuropsychopharmacologia Hungarica
Gaël Quesseveur, Alain M Gardier, Bruno P Guiard
Antidepressant drugs such as the serotonin (5-HT)/norepinephrine (NE) and dopamine (DA) reuptake inhibitors activate monoaminergic neurotransmission in various brain regions, such as the amygdala, the frontal cortex or the hippocampus. Although this property is well established, the post-synaptic mechanisms by which these pharmacological agents exert therapeutic activity in major depressive disorders (MDD) is not fully understood. Recent clinical and preclinical studies have indicated that the density and reactivity of glia and more particularly of astrocytes are reduced in MDD patients...
October 2013: Current Drug Targets
Idaira Oliva, Miriam Fernández, Eduardo D Martín
Brain ischemia triggers excessive release of neurotransmitters that mediate neuronal damage following ischemic injury. The striatum is one of the areas most sensitive to ischemia. Release of dopamine (DA) from ischemic neurons is neurotoxic and directly contributes to the cell death in affected areas. Astrocytes are known to be critically involved in the physiopathology of cerebrovascular disease. However, their response to ischemia and their role in neuroprotection in striatum are not completely understood...
October 2013: Neurobiology of Disease
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