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https://www.readbyqxmd.com/read/28214985/melatonin-alleviates-the-epilepsy-associated-impairments-in-hippocampal-ltp-and-spatial-learning-through-rescue-of-surface-glur2-expression-at-hippocampal-ca1-synapses
#1
Yue Ma, Xiaolong Sun, Juan Li, Ruihua Jia, Fang Yuan, Dong Wei, Wen Jiang
Epilepsy-associated cognitive impairment is common, and negatively impacts patients' quality of life. However, most antiepileptic drugs focus on the suppression of seizures, and fewer emphasize treatment of cognitive dysfunction. Melatonin, an indolamine synthesized primarily in the pineal grand, is reported to be neuroprotective against several central nervous system disorders. In this study, we investigated whether melatonin could reverse cognitive dysfunction in lithium-pilocarpine treated rats. Chronic treatment with melatonin (8 mg/kg daily for 15 days) after induction of status epilepticus significantly alleviated seizure severity, reduced neuronal death in the CA1 region of the hippocampus, improved spatial learning (as measured by the Morris water maze test), and reversed LTP impairments, compared to vehicle treatment...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28195155/how-native-and-alien-metal-cations-bind-atp-implications-for-lithium-as-a-therapeutic-agent
#2
Todor Dudev, Cédric Grauffel, Carmay Lim
Adenosine triphosphate (ATP), the major energy currency of the cell, exists in solution mostly as ATP-Mg. Recent experiments suggest that Mg(2+) interacts with the highly charged ATP triphosphate group and Li(+) can co-bind with the native Mg(2+) to form ATP-Mg-Li and modulate the neuronal purine receptor response. However, it is unclear how the negatively charged ATP triphosphate group binds Mg(2+) and Li(+) (i.e. which phosphate group(s) bind Mg(2+)/Li(+)) and how the ATP solution conformation depends on the type of metal cation and the metal-binding mode...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28177687/curcumin-protects-neuronal-cells-against-status-epilepticus-induced-hippocampal-damage-through-induction-of-autophagy-and-inhibition-of-necroptosis
#3
Jin Wang, Yuan Liu, Xiao-Hui Li, Xiang-Chang Zeng, Jian Li, Jun Zhou, Bo Xiao, Kai Hu
Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Though the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, two novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders...
December 9, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28138157/forebrain-specific-ablation-of-phospholipase-c%C3%AE-1-causes-manic-like-behavior
#4
Y R Yang, J H Jung, S-J Kim, K Hamada, A Suzuki, H J Kim, J H Lee, O-B Kwon, Y K Lee, J Kim, E-K Kim, H-J Jang, D-S Kang, J-S Choi, C J Lee, J Marshall, H-Y Koh, C-J Kim, H Seok, S H Kim, J H Choi, Y-B Choi, L Cocco, S H Ryu, J-H Kim, P-G Suh
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1(f/f); CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses...
January 31, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28120140/lithium-chloride-promotes-neuronal-differentiation-of-rat-neural-stem-cells-and-enhances-neural-regeneration-in-parkinson-s-disease-model
#5
Li Qi, Yonggang Tang, Wei He, Honghua Pan, Wenxian Jiang, Lin Wang, Weilin Deng
Parkinson's disease (PD) is one of the most common neural degenerative disease, affecting millions of people globally. Great progress has been made in the PD treatment, and one of the most promising one is the stem cell-based therapy. Thus, studies on the differentiation of neural stem cells (NSCs) are important to the advancement in PD therapy. In this study, we used the rat NSCs to elucidate the role of Lithium in the proliferation and differentiation of NSCs by immunostaining against Ki67 and BrdU analysis as well as immunostaining against specific neuronal markers...
January 24, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28109985/the-synthetic-neuroactive-steroid-sge-516-reduces-status-epilepticus-and-neuronal-cell-death-in-a-rat-model-of-soman-intoxication
#6
Alison L Althaus, Hilary S McCarren, Aymen Alqazzaz, Cecelia Jackson, John H McDonough, Carl D Smith, Ethan Hoffman, Rebecca S Hammond, Albert J Robichaud, James J Doherty
Organophosphorus nerve agents (OPNAs) are irreversible inhibitors of acetylcholinesterase that pose a serious threat to public health because of their use as chemical weapons. Exposure to high doses of OPNAs can dramatically potentiate cholinergic synaptic activity and cause status epilepticus (SE). Current standard of care for OPNA exposure involves treatment with cholinergic antagonists, oxime cholinesterase reactivators, and benzodiazepines. However, data from pre-clinical models suggest that OPNA-induced SE rapidly becomes refractory to benzodiazepines...
January 18, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28109561/lithium-reverses-behavioral-and-axonal-transport-related-changes-associated-with-ank3-bipolar-disorder-gene-disruption
#7
Michael G Gottschalk, Melanie P Leussis, Tillmann Ruland, Klaudio Gjeluci, Tracey L Petryshen, Sabine Bahn
Ankyrin 3 (ANK3) has been implicated as a genetic risk factor for bipolar disorder (BD), however the resulting pathophysiological and treatment implications remain elusive. In a preclinical systems biological approach, we aimed to characterize the behavioral and proteomic effects of Ank3 haploinsufficiency and chronic mood-stabilizer treatment in mice. Psychiatric-related behavior was evaluated with the novelty-suppressed feeding (NSF) paradigm, elevated plus maze (EPM) and a passive avoidance task (PAT). Tandem mass spectrometry (MS(E)) was employed for hippocampal proteome profiling...
January 18, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28101475/anticonvulsive-effects-of-licofelone-on-status-epilepticus-induced-by-lithium-pilocarpine-in-wistar-rats-a-role-for-inducible-nitric-oxide-synthase
#8
Seyyed Majid Eslami, Mohammad Mobin Moradi, Mehdi Ghasemi, Ahmad Reza Dehpour
BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE...
December 2016: Journal of Epilepsy Research
https://www.readbyqxmd.com/read/28088383/evaluating-the-role-of-astrocytes-on-%C3%AE-estradiol-effect-on-seizures-of-pilocarpine-epileptic-model
#9
Masoumeh Sarfi, Mahmoud Elahdadi Salmani, Iran Goudarzi, Taghi Lashkar Boluki, Kataneh Abrari
Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40μg/µl) was injected subcutaneously from 48 before to 48h after seizure induction...
January 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28066149/neuroprotective-effect-of-lithium-after-pilocarpine-induced-status-epilepticus-in-mice
#10
Namgue Hong, Yun-Sik Choi, Seong Yun Kim, Hee Jung Kim
Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28035180/bipolar-disorder-associated-microrna-mir-1908-5p-regulates-the-expression-of-genes-functioning-in-neuronal-glutamatergic-synapses
#11
Yoonhee Kim, Yinhua Zhang, Kaifang Pang, Hyojin Kang, Heejoo Park, Yeunkum Lee, Bokyoung Lee, Heon-Jeong Lee, Won-Ki Kim, Dongho Geum, Kihoon Han
Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD...
December 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27999548/low-dose-lithium-stabilizes-human-endothelial-barrier-by-decreasing-mlc-phosphorylation-and-universally-augments-cholinergic-vasorelaxation-capacity-in-a-direct-manner
#12
Bert Bosche, Marek Molcanyi, Soham Rej, Thorsten R Doeppner, Mark Obermann, Daniel J Müller, Anupam Das, Jürgen Hescheler, R Loch Macdonald, Thomas Noll, Frauke V Härtel
Lithium at serum concentrations up to 1 mmol/L has been used in patients suffering from bipolar disorder for decades and has recently been shown to reduce the risk for ischemic stroke in these patients. The risk for stroke and thromboembolism depend not only on cerebral but also on general endothelial function and health; the entire endothelium as an organ is therefore pathophysiologically relevant. Regardless, the knowledge about the direct impact of lithium on endothelial function remains poor. We conducted an experimental study using lithium as pharmacologic pretreatment for murine, porcine and human vascular endothelium...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27999308/downregulation-of-homer1b-c-in-sod1-g93a-models-of-als-a-novel-mechanism-of-neuroprotective-effect-of-lithium-and-valproic-acid
#13
Hai-Zhi Jiang, Shu-Yu Wang, Xiang Yin, Hong-Quan Jiang, Xu-Dong Wang, Jing Wang, Tian-Hang Wang, Yan Qi, Yue-Qing Yang, Ying Wang, Chun-Ting Zhang, Hong-Lin Feng
BACKGROUND: Mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). However, the molecular mechanisms have not been elucidated yet. Homer family protein Homer1b/c is expressed widely in the central nervous system and plays important roles in neurological diseases. In this study, we explored whether Homer1b/c was involved in SOD1 mutation-linked ALS. RESULTS: In vitro studies showed that the SOD1 G93A mutation induced an increase of Homer1b/c expression at both the mRNA and protein levels in NSC34 cells...
December 17, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27917448/lithium-reversibly-inhibits-schwann-cell-proliferation-and-differentiation-without-inducing-myelin-loss
#14
Gonzalo Piñero, Randall Berg, Natalia Denise Andersen, Patricia Setton-Avruj, Paula Virginia Monje
This study was undertaken to examine the bioactivity, specificity, and reversibility of lithium's action on the growth, survival, proliferation, and differentiation of cultured Schwann cells (SCs). In isolated SCs, lithium promoted a state of cell cycle arrest that featured extensive cell enlargement and c-Jun downregulation in the absence of increased expression of myelin-associated markers. In addition, lithium effectively prevented mitogen-induced S-phase entry without impairing cell viability. When lithium was administered together with differentiating concentrations of cyclic adenosine monophosphate (cAMP) analogs, a dramatic inhibition of the expression of the master regulator of myelination Krox-20 was observed...
December 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27882645/long-term-lithium-treatment-increases-intracellular-and-extracellular-brain-derived-neurotrophic-factor-bdnf-in-cortical-and-hippocampal-neurons-at-subtherapeutic-concentrations
#15
Vanessa J De-Paula, Wagner F Gattaz, Orestes V Forlenza
OBJECTIVES: The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion...
December 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27882149/combination-of-endogenous-neural-stem-cell-mobilization-and-lithium-chloride-treatment-for-hydrocephalus-following-intraventricular-hemorrhage
#16
Qiang Yuan, Xing-Yao Bu, Zhao-Yue Yan, Xian-Zhi Liu, Zhen-Yu Wei, Chun-Xiao Ma, Ming-Qi Qu
As there are multiple factors causing hydrocephalus subsequent to intraventricular hemorrhage (IVH), it is difficult to achieve the best treatment effect using a single drug alone. In the present study, the protective effect of combination treatment with granulocyte-colony stimulating factor (G-CSF) and lithium chloride against hydrocephalus after IVH was investigated. A total of 130 adult male Sprague-Dawley rats were divided into five groups, including the IVH control, G-CSF treatment, lithium chloride treatment, combination treatment and sham surgery groups...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27878228/lithium-carbonate-and-coenzyme-q10-reduce-cell-death-in-a-cell-model-of-machado-joseph-disease
#17
C M Lopes-Ramos, T C Pereira, D B Dogini, R Gilioli, I Lopes-Cendes
Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture...
November 21, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27873133/altered-expression-of-cxcl13-and-cxcr5-in-intractable-temporal-lobe-epilepsy-patients-and-pilocarpine-induced-epileptic-rats
#18
Ruohan Li, Limin Ma, Hao Huang, Shu Ou, Jinxian Yuan, Tao Xu, Xinyuan Yu, Xi Liu, Juan Yang, Yangmei Chen, Xi Peng
The mechanisms that underlie the pathogenesis of epilepsy are still unclear. Recent studies have indicated that inflammatory processes occurring in the brain are involved in a common and crucial mechanism in epileptogenesis. C-X-C motif chemokine ligand 13 (CXCL13) and its only receptor, C-X-C motif chemokine receptor 5 (CXCR5), are highly expressed in the central nervous system (CNS) and participate in inflammatory responses. The present study aimed to assess the expression of CXCL13 and CXCR5 in the brain tissues of both patients with intractable epilepsy (IE) and a rat model (lithium-pilocarpine) of temporal lobe epilepsy (TLE) to identify possible roles of the CXCL13-CXCR5 signaling pathway in epileptogenesis...
November 21, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27853172/lithium-promotes-dna-stability-and-survival-of-ischemic-retinal-neurocytes-by-upregulating-dna-ligase-iv
#19
Ying Yang, Nandan Wu, Sijia Tian, Fan Li, Huan Hu, Pei Chen, Xiaoxiao Cai, Lijun Xu, Jing Zhang, Zhao Chen, Jian Ge, Keming Yu, Jing Zhuang
Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level...
November 17, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27832289/glycogen-synthase-kinase-3%C3%AE-regulates-fractalkine-production-by-altering-its-trafficking-from-golgi-to-plasma-membrane-implications-for-alzheimer-s-disease
#20
Almudena Fuster-Matanzo, Jerónimo Jurado-Arjona, Stefano Benvegnù, Esther García, Patricia Martín-Maestro, Raquel Gómez-Sintes, Félix Hernández, Jesús Ávila
Glycogen synthase kinase-3β (GSK-3β) is a serine-threonine kinase implicated in multiple processes and signaling pathways. Its dysregulation is associated with different pathological conditions including Alzheimer's disease (AD). Here we demonstrate how changes in GSK-3β activity and/or levels regulate the production and subsequent secretion of fractalkine, a chemokine involved in the immune response that has been linked to AD and to other different neurological disorders. Treatment of primary cultured neurons with GSK-3β inhibitors such as lithium and AR-A014418 decreased full-length fractalkine in total cell extracts...
March 2017: Cellular and Molecular Life Sciences: CMLS
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