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Lithium neuroprotective

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https://www.readbyqxmd.com/read/28098178/lithium-accumulates-in-neurogenic-brain-regions-as-revealed-by-high-resolution-ion-imaging
#1
Giulia Zanni, Wojciech Michno, Elena Di Martino, Anna Tjärnlund-Wolf, Jean Pettersson, Charlotte Elizabeth Mason, Gustaf Hellspong, Klas Blomgren, Jörg Hanrieder
Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088683/effects-of-protease-activated-receptor-1-inhibition-on-anxiety-and-fear-following-status-epilepticus
#2
Mihail Fedoriuk, Dmytro Isaev, Oleg Krishtal, Gregory L Holmes, Elena Isaeva
Protease-activated receptor 1 (PAR1) is an important contributor to the pathogenesis of a variety of brain disorders associated with a risk of epilepsy development. Using the lithium-pilocarpine model of temporal lobe epilepsy (TLE), we recently showed that inhibition of this receptor during the first ten days after pilocarpine-induced status epilepticus (SE) results in substantial anti-epileptogenic and neuroprotective effects. As PAR1 is expressed in the central nervous system regions of importance for processing emotional reactions, including amygdala and hippocampus, and TLE is frequently associated with a chronic alteration of the functions of these regions, we tested the hypothesis that PAR1 inhibition could modulate emotionally driven behavioral responses of rats experiencing SE...
January 12, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28088383/evaluating-the-role-of-astrocytes-on-%C3%AE-estradiol-effect-on-seizures-of-pilocarpine-epileptic-model
#3
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 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28066149/neuroprotective-effect-of-lithium-after-pilocarpine-induced-status-epilepticus-in-mice
#4
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/27999308/downregulation-of-homer1b-c-in-sod1-g93a-models-of-als-a-novel-mechanism-of-neuroprotective-effect-of-lithium-and-valproic-acid
#5
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/27882645/long-term-lithium-treatment-increases-intracellular-and-extracellular-brain-derived-neurotrophic-factor-bdnf-in-cortical-and-hippocampal-neurons-at-subtherapeutic-concentrations
#6
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/27853172/lithium-promotes-dna-stability-and-survival-of-ischemic-retinal-neurocytes-by-upregulating-dna-ligase-iv
#7
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/27777112/stereological-investigation-of-the-ca1-pyramidal-cell-layer-in-untreated-and-lithium-treated-3xtg-ad-and-wild-type-mice
#8
Evelin L Schaeffer, Sergio Catanozi, Mark J West, Wagner F Gattaz
Pyramidal neuron loss in the hippocampal CA1 region is a very early hallmark of Alzheimer disease (AD). Lithium might be a therapeutic strategy for AD due to its neuroprotective and neurotrophic properties. This study used modern stereological techniques to investigate possible CA1 pyramidal neuron loss in 11-month-old triple transgenic AD (3xTg-AD) mice, and also the effects of therapeutic and subtherapeutic lithium doses on the number and density of CA1 pyramidal neurons and volume of CA1 pyramidal layer in 3xTg-AD and wild-type mice treated from 3 to 11 months of age...
January 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27769874/preventive-effects-of-blueberry-extract-on-behavioral-and-biochemical-dysfunctions-in-rats-submitted-to-a-model-of-manic-behavior-induced-by-ketamine
#9
Gabriela Debom, Marta Gazal, Mayara Sandrielly Pereira Soares, Carlus Augustu Tavares do Couto, Bruna Mattos, Claiton Lencina, Manuella Pinto Kaster, Gabriele Codenonzi Ghisleni, Rejane Tavares, Elizandra Braganhol, Vitor Clasen Chaves, Flávio Henrique Reginatto, Francieli Stefanello, Roselia Maria Spanevello
The aim of the present study was to evaluate the protective effects of blueberry extract on oxidative stress and inflammatory parameters in a model of mania induced by ketamine administration in rats. Male rats were pretreated with blueberry extract (200mg/kg, once a day for 14days), lithium chloride (45mg/kg, mood stabilizer used as a positive control, twice a day for 14days), or vehicle. Between the 8th and 14th days, rats also received an injection of ketamine (25mg/kg) or vehicle. In the 15th day, thirty minutes after ketamine administration the hyperlocomotion of the animals was assessed in the open - field apparatus...
October 18, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27739937/lithium-posttreatment-confers-neuroprotection-through-glycogen-synthase-kinase-3%C3%AE-inhibition-in-intracerebral-hemorrhage-rats
#10
Jian Zheng, Zhen Liu, Weishan Li, Jiaxin Tang, Dongwei Zhang, Xiaobo Tang
OBJECTIVE Inflammation and apoptosis are two key factors contributing to secondary brain injury after intracerebral hemorrhage (ICH). The objective of this study was to evaluate the effects of lithium posttreatment on behavior, brain atrophy, inflammation, and perihematomal cell death. Furthermore, the authors aimed to determine the role of the pro-apoptotic glycogen synthase kinase-3β (GSK-3β) after experimental ICH. METHODS Male Sprague-Dawley rats (n = 108) were subjected to intracerebral infusion of semicoagulated autologous blood...
October 14, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27638546/therapeutic-mechanisms-of-lithium-in-bipolar-disorder-recent-advances-and-current-understanding
#11
REVIEW
Gin S Malhi, Tim Outhred
Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice...
October 2016: CNS Drugs
https://www.readbyqxmd.com/read/27579184/microrna-132-interact-with-p250gap-cdc42-pathway-in-the-hippocampal-neuronal-culture-model-of-acquired-epilepsy-and-associated-with-epileptogenesis-process
#12
Jinxian Yuan, Hao Huang, Xin Zhou, Xi Liu, Shu Ou, Tao Xu, Ruohan Li, Limin Ma, Yangmei Chen
Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27490898/glycyrrhizin-ameliorates-oxidative-stress-and-inflammation-in-hippocampus-and-olfactory-bulb-in-lithium-pilocarpine-induced-status-epilepticus-in-rats
#13
Susana González-Reyes, Juan Jair Santillán-Cigales, Angélica Saraí Jiménez-Osorio, José Pedraza-Chaverri, Rosalinda Guevara-Guzmán
Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL's effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE)...
October 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27468233/a-new-look-at-an-old-drug-neuroprotective-effects-and-therapeutic-potentials-of-lithium-salts
#14
REVIEW
Liliana Dell'Osso, Claudia Del Grande, Camilla Gesi, Claudia Carmassi, Laura Musetti
Increasing evidence highlights bipolar disorder as being associated with impaired neurogenesis, cellular plasticity, and resiliency, as well as with cell atrophy or loss in specific brain regions. This has led most recent research to focus on the possible neuroprotective effects of medications, and particularly interesting findings have emerged for lithium. A growing body of evidence from preclinical in vitro and in vivo studies has in fact documented its neuroprotective effects from different insults acting on cellular signaling pathways, both preventing apoptosis and increasing neurotrophins and cell-survival molecules...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27468164/involvement-of-pi3k-akt-gsk-3%C3%AE-and-mtor-in-the-antidepressant-like-effect-of-atorvastatin-in-mice
#15
Fabiana Kalyne Ludka, Leandra Celso Constantino, Tharine Dal-Cim, Luisa Bandeira Binder, Andréa Zomkowski, Ana Lúcia S Rodrigues, Carla Inês Tasca
Atorvastatin is a cholesterol-lowering statin that has been shown to exert several pleiotropic effects in the nervous system as a neuroprotective and antidepressant-like agent. Antidepressant-like effect of atorvastatin in mice is mediated by glutamatergic and serotoninergic receptors, although the precise intracellular signaling pathways involved are unknown. PI3K/Akt/GSK-3β/mTOR signaling pathway has been associated to neurobiology of depression and seems to be modulated by some pharmacological antidepressant strategies...
November 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27351600/the-influence-of-lithium-on-hippocampal-volume-in-elderly-bipolar-patients-a-study-using-voxel-based-morphometry
#16
S Zung, F L Souza-Duran, M G Soeiro-de-Souza, R Uchida, C M Bottino, G F Busatto, H Vallada
Recent studies have demonstrated that lithium (Li) exerts neuronal protective and regenerative effects both in vitro and in vivo. However, the effects of long-term Li treatment in the brain areas associated with memory impairment of elderly bipolar patients are still unknown. The aim of this study was to compare the hippocampal volumes of elderly bipolar patients using Li, elderly bipolar patients not using Li and healthy controls. Sociodemographic, clinical and magnetic resonance imaging data from 30 elderly euthymic bipolar patients who had been using Li for an average of >61 months; 27 elderly euthymic bipolar patients not taking Li for an average of 45 months; and 22 elderly healthy controls were analyzed...
2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27343358/the-neuroprotective-effect-of-lithium-against-high-dose-methylphenidate-possible-role-of-bdnf
#17
Majid Motaghinejad, Zeinab Seyedjavadein, Manijeh Motevalian, Majid Asadi
No abstract text is available yet for this article.
June 22, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27241942/protective-effect-of-lithium-chloride-against-hypoglycemia-induced-apoptosis-in-neuronal-pc12-cell
#18
Yuzhen Xu, Qian Wang, Dongsheng Li, Zhenghua Wu, Dawei Li, Kaili Lu, Yuwu Zhao, Yongning Sun
Hypoglycemia is defined by an arbitrary plasma glucose level lower than 3.9mmol/L and is a most common and feared adverse effect of treatment of diabetes mellitus. Emerging evidences demonstrated that hypoglycemia could induce enhanced apoptosis. Lithium chloride (LiCl), a FDA approved drug clinically used for treatment of bipolar disorders, is recently proven having neuroprotection against various stresses in the cellular and animal models of neural disorders. Here, we have established a hypoglycemia model in vitro and assessed the neuroprotective efficacy of LiCl against hypoglycemia-induced apoptosis and the underlying cellular and molecular mechanisms...
August 25, 2016: Neuroscience
https://www.readbyqxmd.com/read/27237705/hippocampal-subfield-volumes-in-short-and-long-term-lithium-treated-patients-with-bipolar-i-disorder
#19
Alessio Simonetti, Gabriele Sani, Claudia Dacquino, Fabrizio Piras, Pietro De Rossi, Carlo Caltagirone, William Coryell, Gianfranco Spalletta
OBJECTIVES: Patients diagnosed with bipolar disorder (BP) may experience hippocampal atrophy. Lithium exposure has been associated with increased hippocampal volumes. However, its effects on hippocampal subfields remain to be clarified. METHODS: We investigated the effects of short- and long-term lithium exposure on the hippocampus and its subfields in patients affected by bipolar I disorder (BP-I). Hippocampal subfields and total hippocampal volumes were measured in 60 subjects divided into four groups: 15 patients with BP-I who were never exposed to lithium [no-exposure group (NE)], 15 patients with BP-I exposed to lithium for < 24 months [short-exposure group (SE)], 15 patients with BP-I exposed to lithium for > 24 months [long-exposure group (LE)], and 15 healthy control subjects (HC)...
June 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27188468/the-role-of-gastrodin-on-hippocampal-neurons-after-n-methyl-d-aspartate-excitotoxicity-and-experimental-temporal-lobe-seizures
#20
Shi-Bing Wong, Wei-Chen Hung, Ming-Yuan Min
Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure-sensitive gerbils...
June 30, 2016: Chinese Journal of Physiology
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