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Lithium neurons

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https://www.readbyqxmd.com/read/28803243/lithium-sensitivity-of-store-operated-ca2-entry-and-survival-of-fibroblasts-isolated-from-chorea-acanthocytosis-patients
#1
Lisann Pelzl, Bhaeldin Elsir, Itishri Sahu, Rosi Bissinger, Yogesh Singh, Basma Sukkar, Sabina Honisch, Ludger Schoels, Mohamed Jemaà, Elisabeth Lang, Alexander Storch, Andreas Hermann, Christos Stournaras, Florian Lang
BACKGROUND: The widely expressed protein chorein fosters activation of the phosphoinositide 3 kinase (PI3K) pathway thus supporting cell survival. Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes. In mice, genetic knockout of chorein leads to enhanced neuronal apoptosis. PI3K dependent signalling upregulates Orai1, a pore forming channel protein accomplishing store operated Ca2+ entry (SOCE)...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28763058/a-novel-preventive-therapy-for-paclitaxel-induced-cognitive-deficits-preclinical-evidence-from-c57bl-6-mice
#2
P Huehnchen, W Boehmerle, A Springer, D Freyer, M Endres
Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet medical need. Patients often report a cognitive decline in temporal correlation to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial abilities. We treated adult C57Bl/6 mice with 12 × 20 mg kg(-1) paclitaxel (PTX), mimicking clinical conditions of dose-dense chemotherapy, followed by a pulse of bromodesoxyuridine (BrdU) to label dividing cells. In this model, mice developed visuo-spatial memory impairments, and we measured peak PTX concentrations in the hippocampus of 230 nm l(-1), which was sevenfold higher compared with the neocortex...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28758946/hippocampal-proteome-of-rats-subjected-to-the-li-pilocarpine-epilepsy-model-and-the-effect-of-carisbamate-treatment
#3
José Eduardo Marques-Carneiro, Daniele Suzete Persike, Julia Julie Litzahn, Jean-Christophe Cassel, Astrid Nehlig, Maria José da Silva Fernandes
In adult rats, the administration of lithium-pilocarpine (LiPilo) reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). Carisbamate (CRS) possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment...
July 30, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28743945/lithium-sensitive-orai1-expression-store-operated-ca-2-entry-and-suicidal-death-of-neurons-in-chorea-acanthocytosis
#4
Lisann Pelzl, Stefan Hauser, Bhaeldin Elsir, Basma Sukkar, Itishri Sahu, Yogesh Singh, Philip Höflinger, Rosi Bissinger, Mohamed Jemaà, Christos Stournaras, Ludger Schöls, Florian Lang
Chorea-Acanthocytosis (ChAc), a neurodegenerative disorder, results from loss-of-function-mutations of chorein-encoding gene VPS13A. In tumour cells chorein up-regulates ORAI1, a Ca(2+)-channel accomplishing store operated Ca(2+)-entry (SOCE) upon stimulation by STIM1. Furthermore SOCE could be up-regulated by lithium. The present study explored whether SOCE impacts on neuron apoptosis. Cortical neurons were differentiated from induced pluripotent stem cells generated from fibroblasts of ChAc patients and healthy volunteers...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#5
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627669/recovery-of-spinal-cord-injury-following-electroacupuncture-in-rats-through-enhancement-of-wnt-%C3%AE-catenin-signaling
#6
Junfeng Zhang, Shisheng Li, Yaochi Wu
Electroacupuncture (EA) has been demonstrated to promote the functional recovery of neurons following spinal cord injury (SCI); however, the mechanisms underlying its effects have yet to be elucidated. The Wnt/β-catenin signaling pathway has been implicated in the regulation of the balance between growth, proliferation and differentiation of neural precursor cells. The present study aimed to investigate the effects of EA therapy on Wnt/β‑catenin‑regulated gene expression and neuronal recovery in rats with SCI...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624183/the-neuroprotective-effect-of-perampanel-in-lithium-pilocarpine-rat-seizure-model
#7
Ting Wu, Katsutoshi Ido, Yoshihide Osada, Sadaharu Kotani, Akira Tamaoka, Takahisa Hanada
PURPOSE: Status epilepticus (SE) causes irreversible neurodegeneration if not terminated quickly. Perampanel (PER), a potent AMPA receptor antagonist, has previously been shown to terminate seizures in the lithium-pilocarpine SE model. In the present study, we assessed whether PER would also prevent neuronal damage in this model. METHODS: SE was induced in rats using lithium chloride and pilocarpine. Initiation of SE was defined as continuous seizures that exhibited as rearing accompanied by bilateral forelimb clonus (Racine score 4)...
June 14, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28621662/chronic-lithium-treatment-elicits-its-antimanic-effects-via-bdnf-trkb-dependent-synaptic-downscaling
#8
Erinn S Gideons, Pei-Yi Lin, Melissa Mahgoub, Ege T Kavalali, Lisa M Monteggia
Lithium is widely used as a treatment for Bipolar Disorder although the molecular mechanisms that underlie its therapeutic effects are under debate. In this study, we show brain-derived neurotrophic factor (BDNF) is required for the antimanic-like effects of lithium but not the antidepressant-like effects in mice. We performed whole cell patch clamp recordings of hippocampal neurons to determine the impact of lithium on synaptic transmission that may underlie the behavioral effects. Lithium produced a significant decrease in α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes due to postsynaptic homeostatic plasticity that was dependent on BDNF and its receptor tropomyosin receptor kinase B (TrkB)...
June 16, 2017: ELife
https://www.readbyqxmd.com/read/28587098/function-of-metallothionein-3-in-neuronal-cells-do-metal-ions-alter-expression-levels-of-mt3
#9
Jamie Bousleiman, Alexa Pinsky, Sohee Ki, Angela Su, Irina Morozova, Sergey Kalachikov, Amen Wiqas, Rae Silver, Mary Sever, Rachel Narehood Austin
A study of factors proposed to affect metallothionein-3 (MT3) function was carried out to elucidate the opaque role MT3 plays in human metalloneurochemistry. Gene expression of Mt2 and Mt3 was examined in tissues extracted from the dentate gyrus of mouse brains and in human neuronal cell cultures. The whole-genome gene expression analysis identified significant variations in the mRNA levels of genes associated with zinc homeostasis, including Mt2 and Mt3. Mt3 was found to be the most differentially expressed gene in the identified groups, pointing to the existence of a factor, not yet identified, that differentially controls Mt3 expression...
May 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28545972/lithium-alleviates-neurotoxic-prion-peptide-induced-synaptic-damage-and-neuronal-death-partially-by-the-upregulation-of-nuclear-target-rest-and-the-restoration-of-wnt-signaling
#10
Zhiqi Song, Wei Yang, Xiangmei Zhou, Lifeng Yang, Deming Zhao
Prion diseases are a group of infectious neurodegenerative diseases characterized by multiple neuropathological hallmarks, including accumulation of PrP(Sc), synaptic damage, and neuronal death. We previously reported that the repressor element 1-silencing transcription factor (REST), a novel neuroprotective marker in neurodegeneration, protects neurons against neurotoxic peptide (PrP106-126)-induced neurotoxicity, but fails to maintain survival following prolonged exposure to PrP106-126. Because Wnt signaling partially induces REST and is activated by lithium, we investigated the effects of lithium on REST in prion diseases...
May 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28528202/microrna-129-5p-inhibits-the-development-of-autoimmune-encephalomyelitis-related-epilepsy-by-targeting-hmgb1-through-the-tlr4-nf-kb-signaling-pathway
#11
Ai-Hua Liu, Ya-Ting Wu, Yu-Ping Wang
The study aimed to explore the effects of microRNA-129-5p (miR-129-5p) on the development of autoimmune encephalomyelitis (AE)-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway in a rat model. AE-related epilepsy models were established. Sprague-Dawley (SD) rats were randomly divided into control, model, miR-129-5p mimics, miR-129-5p inhibitor, HMGB1 shRNA, TLR4/NF-kB (TLR4/NF-kB signaling pathway was inhibited) and miR-129-5p mimics+HMGB1 shRNA groups respectively. Latency to a first epilepsy seizure attack was recorded...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28511952/lithium-ameliorates-lipopolysaccharide-induced-neurotoxicity-in-the-cortex-and-hippocampus-of-the-adult-rat-brain
#12
Muhammad Sohail Khan, Tahir Ali, Muhammad Noman Abid, Myeung Hoon Jo, Amjad Khan, Min Woo Kim, Gwang Ho Yoon, Eun Woo Cheon, Shafiq Ur Rehman, Myeong Ok Kim
Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α)...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28501694/4-4-diisothiocyanatostilbene-2-2-disulfonic-acid-attenuates-spontaneous-recurrent-seizures-and-vasogenic-edema-following-lithium-pilocarpine-induced-status-epilepticus
#13
Tingting Yang, Zhenzhou Lin, Ling Xie, Yao Wang, Suyue Pan
Vasogenic edema induced by blood brain barrier disruption and neuronal loss play an important role in the epileptogenic process. 4,4'- diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) is a commonly used anion channel inhibitor that has been reported to exert an anticonvulsant effect in rat hippocampus in vitro. The present study aimed to investigate whether DIDS could prevent epileptogenic process in rat lithium-pilocarpine model of temporal lobe epilepsy. The tight junction proteins and serum extravasation were examined in the piriform cortex 3days after status epilepticus...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28500272/probing-the-lithium-response-pathway-in-hipscs-implicates-the-phosphoregulatory-set-point-for-a-cytoskeletal-modulator-in-bipolar-pathogenesis
#14
Brian T D Tobe, Andrew M Crain, Alicia M Winquist, Barbara Calabrese, Hiroko Makihara, Wen-Ning Zhao, Jasmin Lalonde, Haruko Nakamura, Glenn Konopaske, Michelle Sidor, Cameron D Pernia, Naoya Yamashita, Moyuka Wada, Yuuka Inoue, Fumio Nakamura, Steven D Sheridan, Ryan W Logan, Michael Brandel, Dongmei Wu, Joshua Hunsberger, Laurel Dorsett, Cordulla Duerr, Ranor C B Basa, Michael J McCarthy, Namrata D Udeshi, Philipp Mertins, Steven A Carr, Guy A Rouleau, Lina Mastrangelo, Jianxue Li, Gustavo J Gutierrez, Laurence M Brill, Nikolaos Venizelos, Guang Chen, Jeffrey S Nye, Husseini Manji, Jeffrey H Price, Colleen A McClung, Hagop S Akiskal, Martin Alda, De-Maw M Chuang, Joseph T Coyle, Yang Liu, Yang D Teng, Toshio Ohshima, Katsuhiko Mikoshiba, Richard L Sidman, Shelley Halpain, Stephen J Haggarty, Yoshio Goshima, Evan Y Snyder
The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in polygenic diseases is generally challenging. However, hiPSCs from BPD patients responsive to lithium offered unique opportunities to discern lithium's target and hence gain molecular insight into BPD. By profiling the proteomics of BDP-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2)...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28495374/metyrapone-prevents-brain-damage-induced-by-status-epilepticus-in-the-rat-lithium-pilocarpine-model
#15
Luis García-García, Ahmed A Shiha, Rubén Fernández de la Rosa, Mercedes Delgado, Ágata Silván, Pablo Bascuñana, Jens P Bankstahl, Francisca Gomez, Miguel A Pozo
The status epilepticus (SE) induced by lithium-pilocarpine is a well characterized rodent model of the human temporal lobe epilepsy (TLE) which is accompanied by severe brain damage. Stress and glucocorticoids markedly contribute to exacerbate neuronal damage induced by seizures but the underlying mechanisms are poorly understood. Herein we sought to investigate whether a single administration of metyrapone (150 mg/kg, i.p.), an 11β-hydroxylase inhibitor, enzyme involved in the peripheral and central synthesis of corticosteroids, had neuroprotective properties in this model...
May 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28461248/simultaneous-triple-therapy-for-the-treatment-of-status-epilepticus
#16
Jerome Niquet, Roger Baldwin, Keith Norman, Lucie Suchomelova, Lucille Lumley, Claude G Wasterlain
Early maladaptive internalization of synaptic GABAA receptors (GABAAR) and externalization of NMDA receptors (NMDAR) may explain the time-dependent loss of potency of standard anti-epileptic drugs (AED) in refractory status epilepticus (SE). We hypothesized that correcting the effects of changes in GABAAR and NMDAR would terminate SE, even when treatment is delayed 40 minutes. SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAAR agonist midazolam, the NMDAR antagonist ketamine and the AED valproate were injected 40 min after SE onset in combination or as monotherapy...
August 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28444637/phase-dependent-astroglial-alterations-in-li-pilocarpine-induced-status-epilepticus-in-young-rats
#17
Adriana Fernanda K Vizuete, Matheus Mittmann Hennemann, Carlos Alberto Gonçalves, Diogo Losch de Oliveira
Epilepsy prevalence is high in infancy and in the elderly population. Lithium-pilocarpine is widely used to induce experimental animal models of epilepsy, leading to similar neurochemical and morphological alterations to those observed in temporal lobe epilepsy. As astrocytes have been implicated in epileptic disorders, we hypothesized that specific astroglial changes accompany and contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days after Li-pilocarpine-induced status epilepticus (SE), corresponding to different phases in this model of epilepsy...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28423937/concordance-of-several-subcellular-interactions-initiates-alzheimer-s-dementia-their-reversal-requires-combination-treatment
#18
REVIEW
W J Fessel
The pathogenesis of Alzheimer's disease involves multiple pathways that, at the macrolevel, include decreased proliferation plus increased loss affecting neurons, astrocytes, and capillaries and, at the subcellular level, involve several elements: amyloid/amyloid precursor protein, presenilins, the unfolded protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented show the intimate, anatomical interactions between neurons, astrocytes, and capillaries; the interactions between the several subcellular factors affecting those cells; and the treatments that are currently available and that might correct dysfunctions in the subcellular factors...
May 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28415676/nitrobenzylthioinosine-mimics-adenosine-to-attenuate-the-epileptiform-discharge-of-hippocampal-neurons-from-epileptic-rats
#19
Hao Huang, Jing Wang, Jun Zhang, Zhong Luo, Dongxu Li, Xiaowei Qiu, Yan Peng, Zhongxiang Xu, Ping Xu, Zucai Xu
Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative nucleoside transporter, could regulate the extracellular adenosine concentration and have protective roles in seizures. However, the protection mechanism of NBTI in seizures remains poorly understood. Here, the expression pattern and subcellular distribution of adenosine A1 receptor were detected by Western blot analysis and double-labeling immunofluorescence staining in Lithium Chloride-Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was recorded using whole-cell patch clamp...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408639/interaction-between-neuronal-calcium-sensor-protein-1-and-lithium-in-pedunculopontine-neurons
#20
Stasia D'Onofrio, James Hyde, Edgar Garcia-Rill
Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Postmortem studies showed increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Lithium (Li(+)) has been shown to effectively treat the mood disturbances in bipolar disorder patients. We previously showed that NCS-1 at low levels increased, and at high levels decreased, gamma oscillations in RAS pedunculopontine neurons (PPN), and that Li(+) decreased these oscillations...
April 2017: Physiological Reports
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