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https://www.readbyqxmd.com/read/28322842/simultaneous-blockade-of-nmda-receptors-and-parp-1-activity-synergistically-alleviate-immunoexcitotoxicity-and-bioenergetics-in-3-nitropropionic-acid-intoxicated-mice-evidences-from-memantine-and-3-aminobenzamide-interventions
#1
Saravana Babu Chidambaram, Ranju Vijayan, Sathiya Sekar, Sugumar Mani, Barathidsan Rajamani, Ramakrishnan Ganapathy
Interlink between excitotoxicity and cellular bioenergetics depletion is implicated as one of the central deteriorative pathways in many neurodegenerative diseases including Huntington's disease (HD). Chronic administration of 3-nitropropionic acid (3-NP) depletes ATP and NAD(+;) and increases TNFα, IL-6 and glutamate content resulting in "immunoexcitotoxicity". Present study was designed to determine whether the combination of memantine (MN) and 3-aminobenzamide (3-AB), PARP inhibitor, can ameliorate immunoexcitotoxicity and improve bioenergetics in a better manner than individual administration against 3-NP intoxication in mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28314819/depressive-like-behaviors-are-regulated-by-nox1-nadph-oxidase-by-redox-modification-of-nmda-receptor-1
#2
Masakazu Ibi, Junjie Liu, Noriaki Arakawa, Shiho Kitaoka, Ai Kawaji, Ken-Ichi Matsuda, Kazumi Iwata, Misaki Matsumoto, Masato Katsuyama, Kai Zhu, Satoshi Teramukai, Tomoyuki Furuyashiki, Chihiro Yabe-Nishimura
Involvement of reactive oxygen species (ROS) has been suggested in the development of psychiatric disorders. NOX1 is a non-phagocytic form of NADPH oxidase whose expression in the nervous system is negligible compared with other NOX isoforms. However, NOX1-derived ROS increase inflammatory pain and tolerance to opioid analgesia. To clarify the role of NOX1 in the brain, we examined depressive-like behaviors in mice deficient in Nox1 (Nox1(-/Y)). Depressive-like behaviors induced by chronic social defeat stress or administration of corticosterone (CORT) were significantly ameliorated in Nox1(-/Y) Generation of ROS was significantly elevated in the prefrontal cortex (PFC) of mice administrated with CORT, while NOX1 mRNA was up-regulated only in the ventral tegmental area (VTA) among brain areas responsible for emotional behaviors...
March 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28284898/role-of-probdnf-and-bdnf-in-dendritic-spine-plasticity-and-depressive-like-behaviors-induced-by-an-animal-model-of-depression
#3
Hui Qiao, Shu-Cheng An, Chang Xu, Xin-Ming Ma
Major depressive disorder (MDD) is one of the most common psychiatric disorder, but the underlying mechanisms are largely unknown. Increasing evidence shows that brain-derived neurotrophic factor (BDNF) plays an important role in the structural plasticity induced by depression. Considering the opposite effects of BDNF and its precursor proBDNF on neural plasticity, we hypothesized that the balance of BDNF and proBDNF plays a critical role in chronic unpredicted mild stress (CUMS)-induced depressive-like behaviors and structural plasticity in the rodent hippocampus...
March 8, 2017: Brain Research
https://www.readbyqxmd.com/read/28269783/modulating-the-balance-of-synaptic-and-extrasynaptic-nmda-receptors-shows-positive-effects-against-amyloid-%C3%AE-induced-neurotoxicity
#4
Yan Huang, Wei Shen, Jie Su, Bin Cheng, Dong Li, Gang Liu, Wen-Xia Zhou, Yong-Xiang Zhang
Alzheimer's disease (AD) patients suffer a disturbance in the balance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway), and, therefore, restoring the balance of GluN2A and GluN2B should be beneficial for AD. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effect on amyloid-β (Aβ)-induced long-term potentiation deficits. Enhancing the activity of GluN2A had a protective effect against Aβ, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect...
March 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28251011/-being-with-a-buddha-a-case-report-of-methoxetamine-use-in-a-united-states-veteran-with-ptsd
#5
Joan M Striebel, Emily E Nelson, Raj K Kalapatapu
Methoxetamine (MXE) is a ketamine analogue with a high affinity for the N-methyl-D-aspartate (NMDA) receptor. MXE is a newly emerging designer drug of abuse and is widely available through on-line sources and is not detected by routine urine drug screens. In this report, we describe a United States (US) veteran with posttraumatic stress disorder (PTSD) and heavy polysubstance use, who injected high dose MXE for its calming effect. Given MXE's structural similarities to ketamine and recent work showing that ketamine reduces PTSD symptoms, we hypothesize that MXE alleviated this veteran's PTSD symptoms through action at the NMDA receptor and via influences on brain-derived neurotrophic factor (BDNF)...
2017: Case Reports in Psychiatry
https://www.readbyqxmd.com/read/28241130/nardostachys-jatamansi-targets-bdnf-trkb-to-alleviate-ketamine-induced-schizophrenia-like-symptoms-in-rats
#6
Anjali Janardhanan, Anjana Sadanand, Arambakkam Janardhanam Vanisree
OBJECTIVE: Schizophrenia, a common neurological disorder appearing in the late teens or early adulthood, is characterized by disorganized thinking, behaviour, and perception of emotions. Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated synaptic plasticity is a major pathological event here due to dysfunction of dopamine and glutamate transmission at NMDA receptors. De-regulated brain-derived neurotrophic factor (BDNF), i.e., its signalling through the tropomyosin receptor kinase B (TrkB) receptor, is a major feature of schizophrenia...
February 28, 2017: Neuropsychobiology
https://www.readbyqxmd.com/read/28210212/differential-behavioral-and-neurobiological-effects-of-chronic-corticosterone-treatment-in-adolescent-and-adult-rats
#7
Jitao Li, Xiaomeng Xie, Youhong Li, Xiao Liu, Xuemei Liao, Yun-Ai Su, Tianmei Si
Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29-49) or adulthood (PND 71-91) and then subjected to behavioral testing or sacrifice for western blot analyses...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28192174/does-genetic-bdnf-deficiency-in-rats-interact-with-neurotransmitter-control-of-prepulse-inhibition-implications-for-schizophrenia
#8
Maarten van den Buuse, Davina Biel, Kathrin Radscheit
Several studies have suggested a role of BDNF in the development of schizophrenia. For example, post-mortem studies have shown significantly reduced levels of BDNF protein expression in the brain of schizophrenia patients. We investigated the relationship between reduced levels of BDNF in the brain and the regulation of prepulse inhibition (PPI), a behavioral endophenotype of schizophrenia. We used BDNF heterozygous mutant rats which display a 50% decrease of mature BDNF protein levels. Previously, we observed normal baseline PPI and responses to the dopamine D1/D2 receptor agonist, apomorphine, in these rats...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28167133/nmda-receptor-adjusted-co-administration-of-ecstasy-and-cannabinoid-receptor-1-agonist-in-the-amygdala-via-stimulation-of-bdnf-trk-b-creb-pathway-in-adult-male-rats
#9
Ghorbangol Ashabi, Mitra-Sadat Sadat-Shirazi, Solmaz Khalifeh, Laleh Elhampour, Mohammad-Reza Zarrindast
Consumption of cannabinoid receptor-1 (CB-1) agonist such as cannabis is widely taken in 3,4- methylenedioxymethamphetamine (MDMA) or ecstasy users; it has been hypothesized that co-consumption of CB-1 agonist might protect neurons against MDMA toxicity. N-methyl-d-aspartate (NMDA) receptors regulate neuronal plasticity and firing rate in the brain through Tyrosine-kinase B (Trk-B) activation. The molecular and electrophysiological association among NMDA and MDMA/Arachidonylcyclopropylamide (ACPA, a selective CB-1 receptor agonist) co-consumption was not well-known...
February 3, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28164368/bdnf-induced-endocannabinoid-release-modulates-neocortical-glutamatergic-neurotransmission
#10
Mason L Yeh, Rajamani Selvam, Eric S Levine
Endocannabinoids (eCBs) and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), are potent neuromodulators found throughout the mammalian neocortex. Both eCBs and BDNF play critical roles in many behavioral and neurophysiological processes and are targets for the development of novel therapeutics. The effects of eCBs and BDNF are primarily mediated by the type 1 cannabinoid (CB1) receptor and the trkB tyrosine kinase receptor, respectively. Our laboratory and others have previously established that BDNF potentiates excitatory transmission by enhancing presynaptic glutamate release and modulating NMDA receptors...
February 6, 2017: Synapse
https://www.readbyqxmd.com/read/28030799/resveratrol-induced-antinociception-is-involved-in-calcium-channels-and-calcium-caffeine-sensitive-pools
#11
Xiaoyu Pan, Jiechun Chen, Weijie Wang, Ling Chen, Lin Wang, Quan Ma, Jianbo Zhang, Lichao Chen, Gang Wang, Meixi Zhang, Hao Wu, Ruochuan Cheng
Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27992087/urokinase-type-plasminogen-activator-modulates-mammalian-circadian-clock-phase-regulation-in-tissue-type-plasminogen-activator-knockout-mice
#12
Joanna M Cooper, Ashutosh Rastogi, Jessica A Krizo, Eric M Mintz, Rebecca A Prosser
Glutamate phase shifts the circadian clock in the mammalian suprachiasmatic nucleus (SCN) by activating NMDA receptors. Tissue-type plasminogen activator (tPA) gates phase shifts by activating plasmin to generate m(ature) BDNF, which binds TrkB receptors allowing clock phase shifts. Here, we investigate phase shifting in tPA knockout (tPA(-/-) ; B6.129S2-Plat(tm1Mlg) /J) mice, and identify urokinase-type plasminogen activator (uPA) as an additional circadian clock regulator. Behavioral activity rhythms in tPA(-/-) mice entrain to a light-dark (LD) cycle and phase shift in response to nocturnal light pulses with no apparent loss in sensitivity...
December 19, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27882447/neonatal-repeated-exposure-to-isoflurane-not-sevoflurane-in-mice-reversibly-impaired-spatial-cognition-at-juvenile-age
#13
Jianhui Liu, Yanhong Zhao, Junjun Yang, Xiaoqing Zhang, Wei Zhang, Peijun Wang
Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1...
February 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27878552/strength-and-aerobic-exercises-improve-spatial-memory-in-aging-rats-through-stimulating-distinct-neuroplasticity-mechanisms
#14
Thais Ceresér Vilela, Alexandre Pastoris Muller, Adriani Paganini Damiani, Tamires Pavei Macan, Sabrina da Silva, Paula Bortoluzzi Canteiro, Alisson de Sena Casagrande, Giulia Dos Santos Pedroso, Renata Tiscoski Nesi, Vanessa Moraes de Andrade, Ricardo Aurino de Pinho
Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27825855/effect-of-co-administration-of-memantine-and-sertraline-on-the-antidepressant-like-activity-and-brain-derived-neurotrophic-factor-bdnf-levels-in-the-rat-brain
#15
Meysam Amidfar, Gislaine Z Réus, João Quevedo, Yong-Ku Kim, Mohammad Arbabi
A developing body of data has drawn attention to the N-methyl-d-aspartate (NMDA) receptor antagonists as potential drugs for the treatment of major depressive disorder (MDD). We investigated the possibility of synergistic interactions between the antidepressant sertraline with the uncompetitive NMDA receptor antagonist, memantine. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with memantine and sertraline alone or in combination in rats. To this aim, rats were chronically treated with memantine (2...
January 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/27816841/heavy-metals-pb-cd-as-and-mehg-as-risk-factors-for-cognitive-dysfunction-a-general-review-of-metal-mixture-mechanism-in-brain
#16
REVIEW
Venkatanaidu Karri, Marta Schuhmacher, Vikas Kumar
Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na(+) - K(+) ATP-ase pump (Cd, MeHg), biological Ca(+2) (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements)...
December 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27765808/rapid-and-sustained-antidepressant-action-of-the-mglu2-3-receptor-antagonist-mgs0039-in-the-social-defeat-stress-model-comparison-with-ketamine
#17
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate receptor antagonist ketamine, the metabotropic glutamate 2/3 receptor antagonist, MGS0039, shows antidepressant effects. However, there are no reports comparing these 2 compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor, TrkB, phospho-TrkB, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (GluA1), postsynaptic density protein 95, and dendritic spine density in selected brain regions were measured...
October 27, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27765467/glutamatergic-neurotransmission-in-the-prefrontal-cortex-mediates-the-suppressive-effect-of-intra-prelimbic-cortical-infusion-of-bdnf-on-cocaine-seeking
#18
Bok Soon Go, Sarah M Barry, Jacqueline F McGinty
Cocaine self-administration induces dysfunctional neuroadaptations in the prefrontal cortex that underlie relapse to cocaine-seeking. Cocaine self-administration disturbs glutamatergic transmission in the nucleus accumbens that is prevented by infusion of brain-derived neurotrophic factor (BDNF) into the prelimbic area of the prefrontal cortex. Intra-prelimbic infusion of BDNF decreases cocaine-seeking in a TrkB-ERK MAP kinase-dependent manner. Neuronal activity triggers an interaction between TrkB receptors and NMDA receptors, leading to ERK activation...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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
#19
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/27634096/fast-acting-antidepressants-rapidly-stimulate-erk-signaling-and-bdnf-release-in-primary-neuronal-cultures
#20
Ashley E Lepack, Eunyoung Bang, Boyoung Lee, Jason M Dwyer, Ronald S Duman
Recent preclinical and clinical studies demonstrate that three functionally different compounds, the NMDA receptor channel blocker ketamine, mGlu2/3 receptor antagonist LY341495, and NMDA receptor glycine site agent GLYX-13 produce rapid and long lasting antidepressant effects. Furthermore, these agents are reported to stimulate ERK and mTORC1 signaling in brain. Here we used rat primary cortical culture neurons to further examine the cellular actions of these agents. The results demonstrate that low concentrations of all three compounds rapidly increase levels of the phosphorylated and activated forms of ERK and a downstream target of mTORC1, p70S6 kinase, in a concentration and time dependent manner...
December 2016: Neuropharmacology
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