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https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#1
Geoffroy Laumet, Wenjun Zhou, Robert Dantzer, Jules D Edralin, XiaoJiao Huo, David P Budac, Jason C O'Connor, Anna W Lee, Cobi J Heijnen, Annemieke Kavelaars
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain...
July 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28688912/inhibition-of-the-kynurenine-pathway-protects-against-reactive-microglial-associated-reductions-in-the-complexity-of-primary-cortical-neurons
#2
Katherine O'Farrell, Eimear Fagan, Thomas J Connor, Andrew Harkin
Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO) which catalyses the conversion of tryptophan to kynurenine. Microglia also express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the production of the free radical producing metabolites, 3-hydroxykynurenine and 3-hydroxyanthranillic acid respectively and subsequently production of the NMDA receptor agonist quinolinic acid. The aim of this study was to examine the effect of IFNγ-stimulated kynurenine pathway (KP) induction in microglia on neurite outgrowth and complexity, and to determine whether alterations could be abrogated using pharmacological inhibitors of the KP...
September 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28640632/gut-microbiota-nitric-oxide-and-microglia-as-prerequisites-for-neurodegenerative-disorders
#3
Joyce K Y Tse
Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g., superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation...
July 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28540665/different-molecular-mechanisms-mediate-direct-or-glia-dependent-prion-protein-fragment-90-231-neurotoxic-effects-in-cerebellar-granule-neurons
#4
Stefano Thellung, Elena Gatta, Francesca Pellistri, Valentina Villa, Alessandro Corsaro, Mario Nizzari, Mauro Robello, Tullio Florio
Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP(Sc)). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca(++)] i increase...
May 25, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28495142/n-methyl-d-aspartate-receptor-mediated-calcium-overload-and-endoplasmic-reticulum-stress-are-involved-in-interleukin-1beta-induced-neuronal-apoptosis-in-rat-hippocampus
#5
Yilong Dong, Allan V Kalueff, Cai Song
Increased levels of interleukin (IL)-1β and its gene expression are implicated in the etiology of Alzheimer's disease (AD). IL-1β activates microglia and stimulates glutamatergic N-methyl-d-aspartate receptor NMDA receptor expression, thereby disturbing intracellular Ca(2+) homeostasis. Ca(2+) disequilibrium, in turn, may trigger endoplasmic reticulum (ER) stress, contributing to overall excitotoxicity and neuronal death that evoke AD. However, it is unclear whether IL-1β-induced neuronal apoptosis is mediated by the glutamatergic system, ER stress and/or Ca(2+) dysfunction...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28386767/increased-quinolinic-acid-in-peripheral-mononuclear-cells-in-alzheimer-s-dementia
#6
Mandy Busse, Vanessa Hettler, Victoria Fischer, Christian Mawrin, Roland Hartig, Henrik Dobrowolny, Bernhard Bogerts, Thomas Frodl, Stefan Busse
The role of monocytes and macrophages in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) is poorly understood. Recently, we have shown that the number of CD14+ monocytes remained constant during healthy aging and in AD patients. Although only little is known about the function of activated macrophages and microglia in AD, one important mechanism involves the expression of quinolinic acid (QUIN), an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist which mediates excitotoxicity especially in the hippocampus...
April 6, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28270592/evidence-that-remodeling-of-insular-cortex-neurovascular-unit-contributes-to-hypertension-related-sympathoexcitation
#7
Fernanda R Marins, Jennifer A Iddings, Marco A P Fontes, Jessica A Filosa
The intermediate region of the posterior insular cortex (intermediate IC) mediates sympathoexcitatory responses to the heart and kidneys. Previous studies support hypertension-evoked changes to the structure and function of neurons, blood vessels, astrocytes and microglia, disrupting the organization of the neurovascular unit (NVU). In this study, we evaluated the functional and anatomical integrity of the NVU at the intermediate IC in the spontaneously hypertensive rat (SHR) and its control the Wistar-Kyoto (WKY)...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28220827/anti-inflammatory-and-anti-excitoxic-effects-of-diethyl-oxopropanamide-an-ethyl-pyruvate-bioisoster-exert-robust-neuroprotective-effects-in-the-postischemic-brain
#8
Hye-Kyung Lee, Il-Doo Kim, Seung-Woo Kim, Hahnbie Lee, Ju-Young Park, Sung-Hwa Yoon, Ja-Kyeong Lee
Ethyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have robust neuroprotective effects via its anti-inflammatory, anti-oxidative, and anti-apoptotic functions. In an effort to develop novel EP derivatives with greater protective potencies than EP, we generated four EP isosteres, among them the neuroprotective potency of N,N-diethyl-2-oxopropanamide (DEOPA), in which the ethoxy group of EP was replaced with diethylamine, was far greater than that of EP. When DEOPA was administered intravenously (5 mg/kg) to rat middle cerebral artery occlusion (MCAO) model at 6 hrs post-surgery, it suppressed infarct formation, ameliorated neurological and sensory/motor deficits, and inhibited microglial activation and neutrophil infiltrations in the postischemic brain more effectively than EP...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28120640/blockade-of-nmda-receptors-decreased-spinal-microglia-activation-in-bee-venom-induced-acute-inflammatory-pain-in-rats
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
February 2017: 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
#17
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
#18
REVIEW
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
#19
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
#20
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 2017: Molecular Neurobiology
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