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https://www.readbyqxmd.com/read/28845163/neuroprotection-in-schizophrenia-and-its-therapeutic-implications
#1
REVIEW
Yong-Ku Kim, Kyoung-Sae Na
Schizophrenia is a chronic and debilitating mental disorder. The persisting negative and cognitive symptoms that are unresponsive to pharmacotherapy reveal the impairment of neuroprotective aspects of schizophrenia. In this review, of the several neuroprotective factors, we mainly focused on neuroinflammation, neurogenesis, and oxidative stress. We conducted a narrative and selective review. Neuroinflammation is mainly mediated by pro-inflammatory cytokines and microglia. Unlike peripheral inflammatory responses, neuroinflammation has a role in various neuronal activities such as neurotransmission neurogenesis...
July 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28840509/kynurenic-acid-prevents-cytoskeletal-disorganization-induced-by-quinolinic-acid-in-mixed-cultures-of-rat-striatum
#2
Paula Pierozan, Helena Biasibetti-Brendler, Felipe Schmitz, Fernanda Ferreira, Regina Pessoa-Pureur, Angela T S Wyse
Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28836378/ethyl-pyruvate-does-not-require-microglia-for-mediating-neuroprotection-after-excitotoxic-injury
#3
Philipp Pieroh, Daniel-Christoph Wagner, Chalid Ghadban, Gerd Birkenmeier, Faramarz Dehghani
AIMS: Ethyl pyruvate (EP) mediates protective effects after neuronal injury. Besides a direct conservation of damaged neurons, the modulation of indigenous glial cells has been suggested as one important mechanism for EP-related neuroprotection. However, the specific contribution of glial cells is still unknown. METHODS: Organotypic hippocampal slice cultures (OHSC) were excitotoxically lesioned by 50 μmol/L N-methyl-D-aspartate (NMDA, for 4 hours) or left untreated...
August 23, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28836295/microglia-may-compensate-for-dopaminergic-neuron-loss-in-experimental-parkinsonism-through-selective-elimination-of-glutamatergic-synapses-from-the-subthalamic-nucleus
#4
Hitomi Aono, Mohammed Emamussalehin Choudhury, Hiromi Higaki, Kazuya Miyanishi, Yuka Kigami, Kohdai Fujita, Jun-Ichi Akiyama, Hisaaki Takahashi, Hajime Yano, Madoka Kubo, Noriko Nishikawa, Masahiro Nomoto, Junya Tanaka
Parkinson's disease (PD) symptoms do not become apparent until most dopaminergic neurons in the substantia nigra pars compacta (SNc) degenerate, suggesting that compensatory mechanisms play a role. Here, we investigated the compensatory involvement of activated microglia in the SN pars reticulata (SNr) and the globus pallidus (GP) in a 6-hydroxydopamine-induced rat hemiparkinsonism model. Activated microglia accumulated more markedly in the SNr than in the SNc in the model. The cells had enlarged somata and expressed phagocytic markers CD68 and NG2 proteoglycan in a limited region of the SNr, where synapsin I- and postsynaptic density 95-immunoreactivities were reduced...
August 24, 2017: Glia
https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#5
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28817786/propofol-attenuates-bv2-microglia-inflammation-via-nmda-receptor-inhibition
#6
Qichao Wu, Yanjun Zhao, Xiangyuan Chen, Minmin Zhu, Changhong Miao
Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells...
August 17, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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