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Lithium neurons

Yu Mao, Qiuyue Kong, Rongrong Li, Xiaojin Zhang, Yali Gui, Yuehua Li, Chuanfu Li, Yanlin Zhao, Li Liu, Zhengnian Ding
Heat shock protein A12A (HSPA12A) is a newly discovered member of the Hsp70 family. The biological characteristics and functional roles of HSPA12A are poorly understood. This study investigated the effects of HSPA12A on ischaemic stroke in mice. Ischaemic stroke was induced by left middle cerebral artery occlusion for 1 h followed by blood reperfusion. We observed that HSPA12A was highly expressed in brain neurons, and neuronal HSPA12A expression was downregulated by ischaemic stroke and stroke-associated risk factors (aging, obesity and hyperglycaemia)...
March 9, 2018: Biochimica et Biophysica Acta
Anke Hoffmann, Vincenza Sportelli, Michael Ziller, Dietmar Spengler
Bipolar disease (BD) is one of the major public health burdens worldwide and more people are affected every year. Comprehensive genetic studies have associated thousands of single nucleotide polymorphisms (SNPs) with BD risk; yet, very little is known about their functional roles. Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype in disease-relevant tissues and cell types. Neural cells generated from BD-specific iPSCs are thought to capture associated genetic risk factors, known and unknown, and to allow the analysis of their effects on cellular and molecular phenotypes...
March 8, 2018: International Journal of Molecular Sciences
Roxanne J Wadia, Marilyn Stolar, Clarice Grens, Barbara E Ehrlich, Herta H Chao
Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment...
January 26, 2018: Oncotarget
Shinobu Fukumura, Masanori Sasaki, Yuko Kataoka-Sasaki, Shinichi Oka, Masahito Nakazaki, Hiroshi Nagahama, Tomonori Morita, Takuro Sakai, Hiroyuki Tsutsumi, Jeffery D Kocsis, Osamu Honmou
OBJECTIVE: Status epilepticus (SE) causes neuronal cell death, aberrant mossy fiber sprouting (MFS), and cognitive deteriorations. The present study tested the hypothesis that systemically infused mesenchymal stem cells (MSCs) reduce epileptogenesis by inhibiting neuronal cell death and suppressing aberrant MFS, leading to cognitive function preservation in a rat model of epilepsy. METHODS: SE was induced using the lithium-pilocarpine injection model. The seizure frequency was scored using a video-monitoring system and the Morris water maze test was carried out to evaluate cognitive function...
February 14, 2018: Epilepsy Research
Chiara C Bortolasci, Briana Spolding, Edward Callaly, Sheree Martin, Bruna Panizzutti, Srisaiyini Kidnapillai, Timothy Connor, Kyoko Hasebe, Mohammadreza Mohebbi, Olivia M Dean, Sean L McGee, Seetal Dodd, Laura Gray, Michael Berk, Ken Walder
Background: Bipolar disorder (BD) is a mental health condition with progressive social and cognitive function disturbances. Most patients' treatments are based on polypharmacy, but with no biological basis and little is known of the drugs' interactions. The aim of this study was to analyse the effects of lithium, valproate, quetiapine and lamotrigine, and the interactions between them, on markers of inflammation, bioenergetics, mitochondrial function and oxidative stress in neuron-like cells (NT2) and microglial cells...
February 19, 2018: International Journal of Neuropsychopharmacology
Jerónimo Auzmendi, Bruno Buchholz, Jimena Salguero, Carlos Cañellas, Jazmín Kelly, Paula Men, Marcela Zubillaga, Alicia Rossi, Amalia Merelli, Ricardo J Gelpi, Alberto J Ramos, Alberto Lazarowski
Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE...
February 16, 2018: Pharmaceuticals
Sarah A Monaco, Brielle R Ferguson, Wen-Jun Gao
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders. This study examines the effects of lithium on GSK3β and its interaction with β-catenin and NMDA receptors within the prefrontal cortex. Lithium, a clinically relevant drug commonly prescribed as a mood stabilizer for psychiatric disorders, significantly increased levels of phosphorylated GSK3β serine 9, an inhibitory phosphorylation site, and decreased β-catenin ser33/37/thr41 phosphorylation in vitro , indicating GSK3β inhibition and reduced β-catenin degradation...
2018: Frontiers in Cellular Neuroscience
Francesca Biagioni, Michela Ferrucci, Larisa Ryskalin, Federica Fulceri, Gloria Lazzeri, Maria Teresa Calierno, Carla L Busceti, Riccardo Ruffoli, Francesco Fornai
In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course...
December 1, 2017: Archives Italiennes de Biologie
Baoman Li, Jiaan Ren, Li Yang, Xiaowei Li, Guangfeng Sun, Maosheng Xia
Spinal cord injury (SCI) is a type of long-term disability with a high morbidity rate in clinical settings for which there is no effective clinical treatment to date. Usually, lithium is used as a popular mood stabilizer. Recently, growing evidence has shown that lithium has clear neuroprotective effects after SCI, and the administration of lithium can effectively improve locomotor recovery. However, the exact neuroprotective mechanism of lithium is still not understood. Glycogen synthase kinase-3 beta (GSK3β) is a serine/threonine kinase that plays an important role in the neuroprotective effects of lithium both in vivo and in vitro...
February 5, 2018: Neurochemical Research
Shayri G Greenwood, Laura Montroull, Marta Volosin, Helen E Scharfman, Kenneth K Teng, Matthew Light, Risa Torkin, Fredrick Maxfield, Barbara L Hempstead, Wilma J Friedman
Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death...
January 2018: ENeuro
D Wu, X Han, J Feng, Y J Song
Objective: To investigate the expression changes of high mobility group box-1 (HMGB1) and the 2B receptor of N- methyl -D- aspartate receptor (NR2B) in status epilepticus (SE). Methods: (1) Primary hippocampal neurons from SD rats with 16 to 18 days of fetal age were cultured in vitro for 7 days, and exposed to Mg(2+) free media for 3 hours. Those cultured neurons were randomly divided into control group and intermittent hypoxia group. (2) SD rats with similar weight were selected and randomly divided into control group and SE model group...
January 2, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Heather Wei, Dominic Landgraf, George Wang, Michael J McCarthy
Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP6) has effects on circadian rhythms...
January 10, 2018: Cellular Signalling
Rodrigo Machado-Vieira
BACKGROUND: Lithium is the lightest metal and the only mood stabilizer that has been used for over half a century for the treatment of bipolar disorder (BD). As a small ion, lithium is omnipresent, and consequently, its molecular mechanisms and targets are widespread. Currently, lithium is a crucial pharmacotherapy for the treatment of acute mood episodes, prophylactic therapy, and suicide prevention in BD. Besides, lithium blood level is the most widely used biomarker in clinical psychiatry...
December 22, 2017: Journal of Affective Disorders
Manoj P Dandekar, Samira S Valvassori, Gustavo Colombo Dal-Pont, Joao Quevedo
BACKGROUND: Bipolar disorder (BD) is a debilitating mental ailment characterized by recurrent episodes of mania and depression. Primary mood-stabilizing drugs like lithium and valproate alleviate the hypomanic or mild to moderate manic episodes in patients with BD. One of the extensively studied underlying mechanisms for these pharmacological interventions is inhibition of intracellular signaling cascades associated with glycogen synthase kinase-3 beta (GSK-3β), a multi-functional serine-threonine kinase...
December 27, 2017: Current Drug Metabolism
Minji Tong, Zili He, Xiaoxiao Lin, Yulong Zhou, Qingqing Wang, Zengming Zheng, Jian Chen, Huazi Xu, Naifeng Tian
Blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen-glucose deprivation. We evaluated BSCB status using the Evans Blue dye extravasation test and measurement of tight junction (TJ) protein levels; we also assessed functional locomotor recovery...
December 21, 2017: Biochemical and Biophysical Research Communications
Eunsoo Won, Yong-Ku Kim
Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium's specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3β, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed...
December 11, 2017: International Journal of Molecular Sciences
Luis García-García, Rubén Fernández de la Rosa, Mercedes Delgado, Ágata Silván, Pablo Bascuñana, Jens P Bankstahl, Francisca Gomez, Miguel A Pozo
Intracerebral administration of the potassium channel blocker 4-aminopyridine (4-AP) triggers neuronal depolarization and intense acute seizure activity followed by neuronal damage. We have recently shown that, in the lithium-pilocarpine rat model of status epilepticus (SE), a single administration of metyrapone, an inhibitor of the 11β-hydroxylase enzyme, had protective properties of preventive nature against signs of brain damage and neuroinflammation. Herein, our aim was to investigate to which extent, pretreatment with metyrapone (150 mg/kg, i...
February 2018: Neurochemistry International
Florian Lang, Lisann Pelzl, Ludger Schöls, Andreas Hermann, Michael Föller, Tilman E Schäffer, Christos Stournaras
Chorea-acanthocytosis (ChAc), a neurodegenerative disease, results from loss-of-function-mutations of the chorein-encoding gene VPS13A. Affected patients suffer from a progressive movement disorder including chorea, parkinsonism, dystonia, tongue protrusion, dysarthria, dysphagia, tongue and lip biting, gait impairment, progressive distal muscle wasting, weakness, epileptic seizures, cognitive impairment, and behavioral changes. Those pathologies may be paralleled by erythrocyte acanthocytosis. Chorein supports activation of phosphoinositide-3-kinase (PI3K)-p85-subunit with subsequent up-regulation of ras-related C3 botulinum toxin substrate 1 (Rac1) activity, p21 protein-activated kinase 1 (PAK1) phosphorylation, and activation of several tyrosine kinases...
2017: Neuro-Signals
Eun-Jin Kim, Dong Kun Lee, Seong-Geun Hong, Jaehee Han, Dawon Kang
Earlier studies have demonstrated that the tandem pore domain weak inward rectifying K⁺ channel (TWIK)-related K⁺ (TREK)-1 channel is inhibited by antidepressants and is associated with major depression. However, little is known about the effect of mood stabilizers that are commonly used for treatment of bipolar disorder on TREK channels, members of the two-pore domain K⁺ (K2P ) channel family. This study sought to investigate the effect of mood stabilizers on TREK-1 and TREK-2 channels. HEK-293A cells were transfected with human TREK-1 or TREK-2 DNA...
November 19, 2017: International Journal of Molecular Sciences
Razieh Mohammad Jafari, Mohammad Hossein Ghahremani, Nastaran Rahimi, Amir Shadboorestan, Amir Rashidian, Jamileh Esmaeili, Shahram Ejtemaei Mehr, Ahmad Reza Dehpour
The underlying mechanisms for the neuroprotective effects of lithium chloride in neurodegenerative diseases such as seizures remain unknown. In present study the downstream signaling pathway of phospho-ERK/NMDA receptors/nitric oxide has been studied. For this purpose, acute and chronic effect of lithium in seizure animal model and the interaction of NMDA receptor antagonist (MK-801) and neuronal nitric oxide synthase (nNOS) inhibitor (7-NI) with these neuroprotection has been studied. Acute lithium administration showed pro-convulsive properties in pentylenetetrazole (PTZ)-induced seizure model while chronic treatment increased the seizure threshold significantly...
November 2, 2017: Brain Research Bulletin
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