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https://www.readbyqxmd.com/read/27816787/gastrodin-relieved-complete-freund-s-adjuvant-induced-spontaneous-pain-by-inhibiting-inflammatory-response
#1
Ting Sun, Jian Wang, Xiang Li, Yu-Jiao Li, Dan Feng, Wen-Long Shi, Ming-Gao Zhao, Jian-Bo Wang, Yu-Mei Wu
The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma (Gastrodia elata Blume), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N-methyl-d-aspartate (NMDA) receptors, and Ca(2+)/calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC)...
November 3, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27794462/long-term-depression-associated-signaling-is-required-for-an-in-vitro-model-of-nmda-receptor-dependent-synapse-pruning
#2
Maile A Henson, Charles J Tucker, Meilan Zhao, Serena M Dudek
Activity-dependent pruning of synaptic contacts plays a critical role in shaping neuronal circuitry in response to the environment during postnatal brain development. Although there is compelling evidence that shrinkage of dendritic spines coincides with synaptic long-term depression (LTD), and that LTD is accompanied by synapse loss, whether NMDA receptor (NMDAR)-dependent LTD is a required step in the progression toward synapse pruning is still unknown. Using repeated applications of NMDA to induce LTD in dissociated rat neuronal cultures, we found that synapse density, as measured by colocalization of fluorescent markers for pre- and postsynaptic structures, was decreased irrespective of the presynaptic marker used, post-treatment recovery time, and the dendritic location of synapses...
October 26, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27725216/specific-combinations-of-ion-channel-inhibitors-reduce-excessive-ca-2-influx-as-a-consequence-of-oxidative-stress-and-increase-neuronal-and-glial-cell-viability-in-vitro
#3
Ryan L O'Hare Doig, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Sarah A Dunlop, Livia Hool, Melinda Fitzgerald
Combinations of Ca(2+) channel inhibitors have been proposed as an effective means to prevent excess Ca(2+) flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca(2+) concentrations. Here, the effects of combinations of Lomerizine (Lom), 2,3-dioxo-7-(1H-imidazol-1-yl)6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate (YM872), 3,5-dimethyl-1-adamantanamine (memantine (Mem)) and/or adenosine 5'-triphosphate periodate oxidized sodium salt (oxATP) to block voltage-gated Ca(2+) channels, Ca(2+) permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca(2+) concentration and viability of rat primary mixed cortical (MC) cultures exposed to hydrogen peroxide (H2O2) insult, were assessed...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27704743/research-progress-of-the-role-and-mechanism-of-extracellular-signal-regulated-protein-kinase-5-erk5-pathway-in-pathological-pain
#4
Li-Na Yu, Li-Hong Sun, Min Wang, Min Yan
Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27604518/induction-of-hippocampal-long-term-potentiation-increases-the-morphological-dynamics-of-microglial-processes-and-prolongs-their-contacts-with-dendritic-spines
#5
Thomas Pfeiffer, Elena Avignone, U Valentin Nägerl
Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27590141/fasudil-enhances-therapeutic-efficacy-of-neural-stem-cells-in-the-mouse-model-of-mptp-induced-parkinson-s-disease
#6
Yan-Hua Li, Jing-Wen Yu, Jian-Yin Xi, Wen-Bo Yu, Jian-Chun Liu, Qing Wang, Li-Juan Song, Ling Feng, Ya-Ping Yan, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms...
September 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27562096/treatment-of-autistic-spectrum-disorder-with-insulin-like-growth-factors
#7
Raili Riikonen
There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism-based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity-dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD-like behavior defects...
December 0: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/27371338/protective-effects-of-pf-4708671-against-n-methyl-d-aspartic-acid-induced-retinal-damage-in-rats
#8
Ikumi Hayashi, Yuto Aoki, Hiroko Ushikubo, Daiki Asano, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Kunio Ishii
We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia...
December 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27365148/how-does-adenosine-control-neuronal-dysfunction-and-neurodegeneration
#9
Rodrigo A Cunha
The adenosine modulation system mostly operates through inhibitory A1 (A1 R) and facilitatory A2A receptors (A2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: high-frequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A2A R; A2A R switch off A1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change...
July 1, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27352782/microglia-activation-and-schizophrenia-lessons-from-the-effects-of-minocycline-on-postnatal-neurogenesis-neuronal-survival-and-synaptic-pruning
#10
Dragos Inta, Undine E Lang, Stefan Borgwardt, Andreas Meyer-Lindenberg, Peter Gass
The implication of neuroinflammation in schizophrenia, sustained by recent genetic evidence, represents one of the most exciting topics in schizophrenia research. Drugs which inhibit microglia activation, especially the classical tetracycline antibiotic minocycline are currently under investigation as alternative antipsychotics. However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively...
June 27, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27277795/experimental-cortical-spreading-depression-induces-nmda-receptor-dependent-potassium-currents-in-microglia
#11
Stefan Wendt, Emile Wogram, Laura Korvers, Helmut Kettenmann
UNLABELLED: Cortical spreading depression (CSD) is a propagating event of neuronal depolarization, which is considered as the cellular correlate of the migraine aura. It is characterized by a change in the intrinsic optical signal and by a negative DC potential shift. Microglia are the resident macrophages of the CNS and act as sensors for pathological changes. In the present study, we analyzed whether microglial cells might sense CSD by recording membrane currents from microglia in acutely isolated cortical mouse brain slices during an experimentally induced CSD...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27262818/astrocytic-and-microglial-nicotinic-acetylcholine-receptors-an-overlooked-issue-in-alzheimer-s-disease
#12
REVIEW
Saeed Sadigh-Eteghad, Alireza Majdi, Javad Mahmoudi, Samad E J Golzari, Mahnaz Talebi
It is increasingly recognized that astrocytes and microglia-associated dysfunction contribute to AD pathology. In addition, glial nicotinic acetylcholine receptors (nAChRs) play a role in AD-related phenomena, such as neuron survival, synaptic plasticity, and memory. From mechanistic point of view, the glial regulation of pro-inflammatory cytokines, as common contributors in AD, is modulated by nAChRs. Astrocytic and microglial nAChRs contribute to Aβ metabolism, including Aβ phagocytosis and degradation as well as Aβ-related oxidative stress and neurotoxicity...
December 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27228556/neuronal-hyperactivity-disturbs-atp-microgradients-impairs-microglial-motility-and-reduces-phagocytic-receptor-expression-triggering-apoptosis-microglial-phagocytosis-uncoupling
#13
Oihane Abiega, Sol Beccari, Irune Diaz-Aparicio, Agnes Nadjar, Sophie Layé, Quentin Leyrolle, Diego Gómez-Nicola, María Domercq, Alberto Pérez-Samartín, Víctor Sánchez-Zafra, Iñaki Paris, Jorge Valero, Julie C Savage, Chin-Wai Hui, Marie-Ève Tremblay, Juan J P Deudero, Amy L Brewster, Anne E Anderson, Laura Zaldumbide, Lara Galbarriatu, Ainhoa Marinas, Maria dM Vivanco, Carlos Matute, Mirjana Maletic-Savatic, Juan M Encinas, Amanda Sierra
Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response...
May 2016: PLoS Biology
https://www.readbyqxmd.com/read/27189036/in-vivo-administration-of-extracellular-cgmp-normalizes-tnf-%C3%AE-and-membrane-expression-of-ampa-receptors-in-hippocampus-and-spatial-reference-memory-but-not-il-1%C3%AE-nmda-receptors-in-membrane-and-working-memory-in-hyperammonemic-rats
#14
Andrea Cabrera-Pastor, Vicente Hernandez-Rabaza, Lucas Taoro-Gonzalez, Tiziano Balzano, Marta Llansola, Vicente Felipo
Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory...
October 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27155670/does-concurrent-use-of-some-botanicals-interfere-with-treatment-of-tuberculosis
#15
REVIEW
William R Folk, Aaron Smith, Hailong Song, Dennis Chuang, Jianlin Cheng, Zezong Gu, Grace Sun
Millions of individuals with active TB do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. Many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of TB, as suggested by results of a recent clinical trial of the South African botanical Sutherlandia frutescens (L.) R. Br. (Sutherlandia). Here we provide a brief summary of Sutherlandia's effects upon rodent microglia and neurons relevant to tuberculosis of the central nervous system (CNS-TB)...
September 2016: Neuromolecular Medicine
https://www.readbyqxmd.com/read/27094552/interferon-gamma-potentiates-nmda-receptor-signaling-in-spinal-dorsal-horn-neurons-via-microglia-neuron-interaction
#16
Mayumi Sonekatsu, Wataru Taniguchi, Manabu Yamanaka, Naoko Nishio, Shunji Tsutsui, Hiroshi Yamada, Munehito Yoshida, Terumasa Nakatsuka
BACKGROUND: Glia-neuron interactions play an important role in the development of neuropathic pain. Expression of the pro-inflammatory cytokne →cytokine Interferon-gamma (IFNγ) is upregulated in the dorsal horn after peripheral nerve injury, and intrathecal IFNγ administration induces mechanical allodynia in rats. A growing body of evidence suggests that IFNγ might be involved in the mechanisms of neuropathic pain, but its effects on the spinal dorsal horn are unclear. We performed blind whole-cell patch-clamp recording to investigate the effect of IFNγ on postsynaptic glutamate-induced currents in the substantia gelatinosa neurons of spinal cord slices from adult male rats...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27091224/phenylketonuria-direct-and-indirect-effects-of-phenylalanine
#17
Gudrun Schlegel, Ralf Scholz, Kurt Ullrich, René Santer, Gabriele M Rune
High phenylalanine concentrations in the brain due to dysfunctional phenylalanine hydroxylase (Pah) are considered to account for mental retardation in phenylketonuria (PKU). In this study, we treated hippocampal cultures with the amino acid in order to determine the role of elevated levels of phenylalanine in PKU-related mental retardation. Synapse density and dendritic length were dramatically reduced in hippocampal cultures treated with phenylalanine. Changes in cofilin expression and phosphorylation status, which were restored by NMDA, as well as reduced activation of the small GTPase Rac1, likely underlie these structural alterations...
July 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27072742/involvement-of-the-kynurenine-pathway-in-the-pathogenesis-of-parkinson-s-disease
#18
Chai K Lim, Francisco J Fernández-Gomez, Nady Braidy, Cristina Estrada, Cristina Costa, Silvia Costa, Alban Bessede, Emiliano Fernandez-Villalba, Anna Zinger, Maria Trinidad Herrero, Gilles J Guillemin
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and localized neuroinflammation occurring in the midbrain several years before the actual onset of symptoms. Neuroinflammation leads to microglia activation and release of a large number of proinflammatory mediators. The kynurenine pathway (KP) of tryptophan catabolism is one of the major regulators of the immune response and is also likely to be implicated in the inflammatory and neurotoxic events in Parkinsonism...
April 9, 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27046518/role-of-glutamate-receptors-and-glial-cells-in-the-pathophysiology-of-treatment-resistant-depression
#19
Yong-Ku Kim, Kyoung-Sae Na
Treatment-resistant depression (TRD) causes substantial socioeconomic burden. Although a consensus on the definition of TRD has not yet been reached, it is certain that classic monoaminergic antidepressants are ineffective for TRD. One decade ago, many researchers found ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, to be an alternative to classic monoaminergic antidepressants. The major mechanisms of action of ketamine rapidly induce synaptogenesis in the brain-derived neurotrophic factor (BDNF) pathway...
October 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/26969530/anti-nmda-receptor-autoantibodies-and-associated-neurobehavioral-pathology-in-mice-are-dependent-on-age-of-first-exposure-to-toxoplasma-gondii
#20
Geetha Kannan, Joshua A Crawford, ChunXia Yang, Kristin L Gressitt, Chinezimuzo Ihenatu, Irina N Krasnova, Jean Lud Cadet, Robert H Yolken, Emily G Severance, Mikhail V Pletnikov
BACKGROUND: Toxoplasma gondii is a pathogen implicated in psychiatric disorders. As elevated antibodies to T. gondii are also present in non-symptomatic individuals, we hypothesized that the age during first exposure to the pathogen may affect symptom manifestation. We tested this hypothesis by evaluating neurobehavioral abnormalities and the immune response in mice following adolescent or adult T. gondii infection. METHODS: Mice were infected with T. gondii at postnatal day 33 (adolescent/juvenile) or 61 (adult)...
July 2016: Neurobiology of Disease
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