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https://www.readbyqxmd.com/read/28120640/blockade-of-nmda-receptors-decreased-spinal-microglia-activation-in-bee-venom-induced-acute-inflammatory-pain-in-rats
#1
Li Li, Yongfang Wu, Zhifeng Bai, Yuyan Hu, Wenbin Li
OBJECTIVES: Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats...
March 2017: Neurological Research
https://www.readbyqxmd.com/read/28112061/inflammation-and-depression-a-causal-or-coincidental-link-to-the-pathophysiology
#2
Brian E Leonard
This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional...
January 23, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28094536/the-novel-induction-of-retinal-ganglion-cell-apoptosis-in-porcine-organ-culture-by-nmda-an-opportunity-for-the-replacement-of-animals-in-experiments
#3
Sandra Kuehn, Jose Hurst, Adelina Jashari, Kathrin Ahrens, Teresa Tsai, Ilan M Wunderlich, H Burkhard Dick, Stephanie C Joachim, Sven Schnichels
Some of the advantages of retina organ culture models include their efficient and easy handling and the ability to standardise relevant parameters. Additionally, when porcine eyes are obtained from the food industry, no animals are killed solely for research purposes. To induce retinal degeneration, a commonly used toxic substance, N-methyl-D-aspartate (NMDA), was applied to the cultures. To this end, organotypic cultures of porcine retinas were cultured and treated with different doses of NMDA (0 [control], 50, 100 and 200μM) on day 2 for 48 hours...
December 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28092020/early-life-social-isolation-induced-depressive-like-behavior-in-rats-results-in-microglial-activation-and-neuronal-histone-methylation-that-are-mitigated-by-minocycline
#4
Hong-Tao Wang, Fu-Lian Huang, Zhao-Lan Hu, Wen-Juan Zhang, Xiao-Qing Qiao, Yan-Qing Huang, Ru-Ping Dai, Fang Li, Chang-Qi Li
Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests...
January 16, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28039043/cathepsin-s-in-the-spinal-microglia-contributes-to-remifentanil-induced-hyperalgesia-in-rats
#5
L Ye, L Xiao, S Y Yang, J J Duan, Y Chen, Y Cui, Y Chen
Cysteine protease Cathepsin S (CatS) expressed by spinal microglia has been shown to play a critical role in nerve injury and inflammation-induced chronic pain. However, whether microglial CatS contributes to remifentanil-induced acute hyperalgesia remains unstudied. In the present study, intravenous remifentanil infusion induced a significant increase in the expression of premature and mature form of CatS in the activated microglia in the spinal cord. Spinal delivery of irreversible CatS inhibitor LHVS reduced hyperalgesia, attenuated activation of spinal microglia and blocked phosphorylation of NMDA receptor NR1 subunit induced by remifentanil...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27920803/bone-pain-mechanism-in-osteoporosis-a-narrative-review
#6
REVIEW
Consalvo Mattia, Flaminia Coluzzi, Ludovica Celidonio, Renato Vellucci
Bone pain in elderly people dramatically affects their quality of life, with osteoporosis being the leading cause of skeletal related events. Peripheral and central mechanisms are involved in the pathogenesis of the nervous system sensitization. Osteoporosis in the elderly has been associated with increased density of bone sensory nerve fibers and their pathological modifications, together with an over-expression of nociceptors sensitized by the lowering pH due to the osteoclastic activity. The activation of N-methyl-D-aspartate (NMDA) receptors and the microglia, as a response to a range of pathological conditions, represent the leading cause of central sensitization...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27816787/gastrodin-relieved-complete-freund-s-adjuvant-induced-spontaneous-pain-by-inhibiting-inflammatory-response
#7
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)...
December 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
REVIEW
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...
November 2016: 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
#14
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
#15
REVIEW
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...
December 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
#16
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
#17
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
#18
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
#19
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
#20
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
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