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https://www.readbyqxmd.com/read/29163060/nmda-receptors-regulate-the-development-of-neuronal-intrinsic-excitability-through-cell-autonomous-mechanisms
#1
Guoqiang Hou, Zhong-Wei Zhang
Maturation of neuronal and synaptic functions during early life is essential for the development of neuronal circuits and behaviors. In newborns synaptic transmission at excitatory synapses is primarily mediated by N-methyl-D-aspartate receptors (NMDARs), and NMDAR-mediated signaling plays an important role in synaptic maturation. Concomitant with synapse development, the intrinsic properties of neurons undergo dramatic changes during early life. However, little is known about the role of NMDARs in the development of intrinsic excitability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29161812/acute-amino-acid-d-serine-administration-similar-to-ketamine-produces-antidepressant-like-effects-through-the-identical-mechanisms
#2
I-Hua Wei, Kuang-Ti Chen, Mang-Hung Tsai, Ching-Hsiang Wu, Hsien-Yuan Lane, Chih-Chia Huang
D-serine is an amino acid and can work as an agonist at the glycine sites of N-methyl-D-aspartate receptor (NMDAR). Interestingly, both types of glutamatergic modulators, NMDAR enhancers and blockers, can improve depression through common targets, namely alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptors (AMPARs) and mammalian target of rapamycin (mTOR). To elucidate the cellular signaling pathway underlying this counterintuitive observation, we activated NMDARs in rats by using D-serine. Saline, ketamine (NMDAR antagonist), and desipramine (tricyclic antidepressant) were used as controls...
November 22, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#3
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#4
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29156769/liraglutide-activates-autophagy-via-glp-1r-to-improve-functional-recovery-after-spinal-cord-injury
#5
Jian Chen, Zhouguang Wang, Yuqin Mao, Zengming Zheng, Yu Chen, Sinan Khor, Kesi Shi, Zili He, Jiawei Li, Fanghua Gong, Yanlong Liu, Aiping Hu, Jian Xiao, Xiangyang Wang
Therapeutics used to treat central nervous system (CNS) injury are designed to promote axonal regeneration and inhibit cell death. Previous studies have shown that liraglutide exerts potent neuroprotective effects after brain injury. However, little is known if liraglutide treatment has neuroprotective effects after spinal cord injury (SCI). This study explores the neuroprotective effects of liraglutide and associated underlying mechanisms. Our results showed that liraglutide could improve recovery after injury by decreasing apoptosis as well as increasing microtubulin acetylation, and autophagy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151137/blood-brain-barrier-transport-and-neuroprotective-potential-of-blackberry-digested-polyphenols-an-in-vitro-study
#6
Inês Figueira, Lucélia Tavares, Carolina Jardim, Inês Costa, Ana P Terrasso, Andreia F Almeida, Coen Govers, Jurriaan J Mes, Rui Gardner, Jörg D Becker, Gordon J McDougall, Derek Stewart, Augusto Filipe, Kwang S Kim, Dora Brites, Catarina Brito, M Alexandra Brito, Cláudia N Santos
PURPOSE: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols into the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their neuroprotective effects...
November 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29148269/salidroside-attenuates-neuroinflammation-and-improves-functional-recovery-after-spinal-cord-injury-through-microglia-polarization-regulation
#7
Chenggui Wang, Qingqing Wang, Yiting Lou, Jianxiang Xu, Zhenhua Feng, Yu Chen, Qian Tang, Gang Zheng, Zengjie Zhang, Yaosen Wu, Naifeng Tian, Yifei Zhou, Huazi Xu, Xiaolei Zhang
Spinal cord injury (SCI) is a severe neurological disease; however, few drugs have been proved to treat SCI effectively. Neuroinflammation is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Salidroside (Sal) has been reported to exert anti-inflammatory effects in airway, adipose and myocardial tissue; however, the role of Sal in SCI therapeutics has not been clarified. In this study, we showed that Sal could improve the functional recovery of spinal cord in rats as revealed by increased BBB locomotor rating scale, angle of incline, and decreased cavity of spinal cord injury and apoptosis of neurons in vivo...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29147958/ginsenoside-rg1-decreases-oxidative-stress-and-down-regulates-akt-mtor-signalling-to-attenuate-cognitive-impairment-in-mice-and-senescence-of-neural-stem-cells-induced-by-d-galactose
#8
Linbo Chen, Hui Yao, Xiongbin Chen, Ziling Wang, Yue Xiang, Jieyu Xia, Ying Liu, Yaping Wang
Adult hippocampal neurogenesis plays a pivotal role in learning and memory. The suppression of hippocampal neurogenesis induced by an increase of oxidative stress is closely related to cognitive impairment. Neural stem cells which persist in the adult vertebrate brain keep up the production of neurons over the lifespan. The balance between pro-oxidants and anti-oxidants is important for function and surviving of neural stem cells. Ginsenoside Rg1 is one of the most active components of Panax ginseng, and many studies suggest that ginsenosides have antioxidant properties...
November 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29143288/gsk3%C3%AE-controls-mtor-and-prosurvival-signaling-in-neurons
#9
Malgorzata Urbanska, Agata Gozdz, Matylda Macias, Iwona A Cymerman, Ewa Liszewska, Ilona Kondratiuk, Herman Devijver, Benoit Lechat, Fred Van Leuven, Jacek Jaworski
Glycogen synthase kinases-3β (GSK3β) is a key regulator of cell homeostasis. In neurons, GSK3β contributes to control of neuronal transmission and plasticity. Despite extensive studies in non-neuronal cells, crosstalk between GSK3β and other signaling pathways remains not well defined in neurons. In the present study, we report that GSK3β positively affected the activity of effectors of mammalian target of rapamycin complex 1 (mTORC1) and complex 2 (mTORC2), in mature neurons in vitro and in vivo. GSK3β also promoted prosurvival signaling and attenuated kainic acid-induced apoptosis...
November 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29141229/widespread-translational-remodeling-during-human-neuronal-differentiation
#10
John D Blair, Dirk Hockemeyer, Jennifer A Doudna, Helen S Bateup, Stephen N Floor
Faithful cellular differentiation requires temporally precise activation of gene expression programs, which are coordinated at the transcriptional and translational levels. Neurons express the most complex set of mRNAs of any human tissue, but translational changes during neuronal differentiation remain incompletely understood. Here, we induced forebrain neuronal differentiation of human embryonic stem cells (hESCs) and measured genome-wide RNA and translation levels with transcript-isoform resolution. We found that thousands of genes change translation status during differentiation without a corresponding change in RNA level...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29136407/phospholipase-d-inhibitors-reduce-human-prostate-cancer-cell-proliferation-and-colony-formation
#11
Amanda R Noble, Norman J Maitland, Daniel M Berney, Martin G Rumsby
BACKGROUND: Phospholipases D1 and D2 (PLD1/2) hydrolyse cell membrane glycerophospholipids to generate phosphatidic acid, a signalling lipid, which regulates cell growth and cancer progression through effects on mTOR and PKB/Akt. PLD expression and/or activity is raised in breast, colorectal, gastric, kidney and thyroid carcinomas but its role in prostate cancer (PCa), the major cancer of men in the western world, is unclear. METHODS: PLD1 protein expression in cultured PNT2C2, PNT1A, P4E6, LNCaP, PC3, PC3M, VCaP, 22RV1 cell lines and patient-derived PCa cells was analysed by western blotting...
November 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29136244/a-molecular-cascade-modulates-map1b-and-confers-resistance-to-mtor-inhibition-in-human-glioblastoma
#12
Dan R Laks, Juan A Oses-Prieto, Alvaro G Alvarado, Jonathan Nakashima, Shreya Chand, Daniel B Azzam, Ankur A Gholkar, Jantzen Sperry, Kirsten Ludwig, Michael C Condro, Serli Nazarian, Anjelica Cardenas, Michelle Y S Shih, Robert Damoiseaux, Bryan France, Nicholas Orozco, Koppany Visnyei, Thomas J Crisman, Fuying Gao, Jorge Z Torres, Giovanni Coppola, Alma L Burlingame, Harley I Kornblum
Background: Clinical trials of therapies directed against nodes of the PI3K/AKT/mTOR signaling axis in Glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin and our analysis implicated a role for GSK3B attenuation in mediating resistance that was confirmed by functional studies...
November 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29131026/trpml1-participates-in-the-progression-of-alzheimer-s-disease-by-regulating-the-ppar%C3%AE-ampk-mtor-signalling-pathway
#13
Lu Zhang, Yu Fang, Xuan Cheng, Yajun Lian, Hongliang Xu, Zhaoshu Zeng, Hongcan Zhu
BACKGROUND: TRPML1 is reported to be involved in the pathogenesis of Alzheimer's disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. METHODS: We developed an APP/PS1 transgenic animal model that presents with AD. TRPML1 was also overexpressed in these mice. Protein expression levels were determined by Western blot. Morris water maze (MWM) and recognition tasks were performed to characterize cognitive ability. TUNEL assays were analysed for the detection of neuronal apoptosis...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130119/p85-regulates-neuronal-migration-through-affecting-neuronal-morphology-during-mouse-corticogenesis
#14
Xinran Cheng, Kaikai Li, MengMeng Liu, Xinde Hu, Mingrui Xu, Runchuan Yan, Shanting Zhao
In mammalian developing embryonic cortex, projection neurons migrate from the ventricular zone to the cortical plate, guided by radial glial cells with a transformation between bipolar and multipolar morphology. Previous studies have demonstrated that the PI3K-Akt-mTOR signal plays a critical role in brain development. However, the function of P85 in cortical development is still unclear. In the present study, we found that overexpression of P85 impaired cortical neuronal migration. Using in utero electroporation, we revealed that the length of the leading process in P85 overexpressed neurons became shorter than that in the control group but with more branches...
November 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29129468/inhibition-of-rac1-ameliorates-neuronal-oxidative-stress-damage-via-reducing-bcl-2-rac1-complex-formation-in-mitochondria-through-pi3k-akt-mtor-pathway
#15
Yundan Pan, Na Wang, Pingping Xia, E Wang, Qulian Guo, Zhi Ye
Although the neuroprotective effects of Rac1 inhibition have been reported in various cerebral ischemic models, the molecular mechanisms of action have not yet been fully elucidated. In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria...
November 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29128905/down-syndrome-ipsc-derived-astrocytes-impair-neuronal-synaptogenesis-and-the-mtor-pathway-in-vitro
#16
Bruno H S Araujo, Carolini Kaid, Janaina S De Souza, Sérgio Gomes da Silva, Ernesto Goulart, Luiz C J Caires, Camila M Musso, Laila B Torres, Adriano Ferrasa, Roberto Herai, Mayana Zatz, Oswaldo K Okamoto, Esper A Cavalheiro
Several methods have been used to study the neuropathogenesis of Down syndrome (DS), such as mouse aneuploidies, post mortem human brains, and in vitro cell culture of neural progenitor cells. More recently, induced pluripotent stem cell (iPSC) technology has offered new approaches in investigation, providing a valuable tool for studying specific cell types affected by DS, especially neurons and astrocytes. Here, we investigated the role of astrocytes in DS developmental disease and the impact of the astrocyte secretome in neuron mTOR signaling and synapse formation using iPSC derived from DS and wild-type (WT) subjects...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29127203/receptor-for-advanced-glycation-endproducts-mediates-sepsis-triggered-amyloid-%C3%AE-accumulation-tau-phosphorylation-and-cognitive-impairment
#17
Juciano Gasparotto, Carolina S Girardi, Nauana Somensi, Camila T Ribeiro, José C F Moreira, Monique Michels, Beatriz Sonai, Mariane Rocha, Amanda V Steckert, Tatiana Barichello, João Quevedo, Felipe Dal-Pizzol, Daniel P Gelain
Patients recovering from sepsis have higher rates of CNS morbidities associated with long-lasting impairment of cognitive functions, including neurodegenerative diseases. However, the molecular etiology of these sepsis-induced impairments is unclear. Here, we investigated the role of the receptor for advanced glycation end products (RAGE) in neuroinflammation, neurodegeneration-associated changes, and cognitive dysfunction arising after sepsis recovery. Adult Wistar rats underwent cecal ligation and perforation (CLP), and serum and brain (hippocampus and prefrontal cortex) samples were obtained at days 1, 15, and 30 after the CLP...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29115495/pirb-inhibits-axonal-outgrowth-via-the-pi3k-akt-mtor-signaling-pathway
#18
Yong-Yan Bi, Yong Quan
Accumulating data strongly suggests that leukocyte immunoglobulin like receptor B1 (PirB) inhibits axonal outgrowth. However, the underlying mechanisms remain unclear. In the present study, cortical neurons of newborn mice were cultured with Nogo‑66 (Nogo‑p4; 4 µmol/l; a PirB ligand) together with NEP1‑40 (Nogo inhibitory peptide) and/or anti‑PirB body (50 mg/ml). PirB mRNA and protein was higher in cultured neurons induced by Nogo‑66 compared with untreated cells. Neurite outgrowth assays demonstrated that the inhibitory effects of Nogo‑66 on axonal outgrowth were reversed by anti‑PirB body...
October 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115479/overexpression-of-mir%C3%A2-185-inhibits-autophagy-and-apoptosis-of-dopaminergic-neurons-by-regulating-the-ampk-mtor-signaling-pathway-in-parkinson-s-disease
#19
Zhi Wen, Jie Zhang, Peng Tang, Ning Tu, Ke Wang, Guangyao Wu
Parkinson's disease (PD) is an age‑associated neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Activation of 5'‑adenosine monophosphate‑activated protein kinase (AMPK) has been suggested to be associated with PD pathogenesis. The aim of the present study was to investigate the effects of the aberrant expression of microRNA‑185 (miR‑185) in PD. A 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑induced in vitro model of PD was generated using the human SH‑SY5Y dopaminergic neuroblastoma cell line, in order to examine the potential molecular mechanisms underlying the roles of miR‑185 in PD...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115424/cornin-protects-sh%C3%A2-sy5y-cells-against-oxygen-and-glucose-deprivation%C3%A2-induced-autophagy-through-the-pi3k-akt-mtor-pathway
#20
Changling Ding, Jie Zhang, Baoyuan Li, Zhaoxing Ding, Wenna Cheng, Fei Gao, Ye Zhang, Yangyang Xu, Shuping Zhang
It has been reported that cornin may reduce neuronal death during cerebral ischemia; however, little is known about the molecular mechanism of the role of corninin autophagy in SH‑SY5Y neuronal cells. In the present study, oxygen‑glucose deprivation (OGD)‑treated cells were used as a cerebral ischemia model in vitro. The results demonstrated that cornin was able to reduce neuronal cell loss, increase the apoptosis regulator Bcl‑2/apoptosis regulator BAX ratio, and decrease the protein levels of caspase‑3...
October 25, 2017: Molecular Medicine Reports
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