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lithium and Alzheimer's

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...
November 10, 2016: Cellular and Molecular Life Sciences: CMLS
Davangere P Devanand, Gregory H Pelton, Kristina D'Antonio, Jesse G Strickler, William C Kreisl, James Noble, Karen Marder, Anne Skomorowsky, Edward D Huey
No abstract text is available yet for this article.
November 4, 2016: Alzheimer Disease and Associated Disorders
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...
October 21, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Theodore Lemuel Mathuram, Vilwanathan Ravikumar, Lisa M Reece, Selvaraju Karthik, Changam Sheela Sasikumar, Kotturathu Mammen Cherian
Neuroblastoma is the most common tumor amongst children amounting to nearly 15% of cancer deaths. This cancer is peculiar in its characteristics, exhibiting differentiation, maturation and metastatic transformation leading to poor prognosis and low survival rates among children. Chemotherapy, though toxic to normal cells, has shown to improve the survival of the patient with emphasis given more towards targeting angiogenesis. Recently, Tideglusib was designed as an 'Orphan Drug' to target the neurodegenerative Alzheimer's disease and gained significant momentum in its function during clinical trials...
September 2016: Environmental Toxicology and Pharmacology
Sandra Guidi, Patrizia Bianchi, Fiorenza Stagni, Andrea Giacomini, Marco Emili, Stefania Trazzi, Elisabetta Ciani, Renata Bartesaghi
In this review we look at this biological overlaps of neurodegenerative and psychiatric conditions, as exemplified by major depressive disorder (MDD). Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress (O&NS), couple to drive changes in neuroregulatory tryptophan catabolite (TRYCAT), with consequences for serotonin availability for the melatonergic pathways. Such work significantly questions the validity and utility of non-biologically based current classification systems for psychiatric and neurodegenerative conditions...
August 1, 2016: CNS & Neurological Disorders Drug Targets
Richard S Jope, Charles B Nemeroff
Lithium, an element that Mother Nature has put in some drinking water sources, has been used for its curative powers for centuries. Today, it's given in capsule form as a mood stabilizer for bipolar disorder and depression. New research, however, reveals its role as a neuroprotector, and suggests that a better understanding of the role enzymes modulated by lithium play could lead to new treatments for Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other neurodegenerative disorders.
January 2016: Cerebrum: the Dana Forum on Brain Science
P Lei, S Ayton, A T Appukuttan, S Moon, J A Duce, I Volitakis, R Cherny, S J Wood, M Greenough, G Berger, C Pantelis, P McGorry, A Yung, D I Finkelstein, A I Bush
Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features...
July 12, 2016: Molecular Psychiatry
B Huisamen, T Lubelwana Hafver, D Lumkwana, A Lochner
PURPOSE: There is an ongoing search for new drugs and drug targets to treat diseases like Alzheimer's disease, cancer and type 2 diabetes (T2D). Both obesity and T2D are characterized by the development of a cardiomyopathy associated with increased hypertension and compensatory left ventricular hypertrophy. Small, specific glycogen synthase kinase-3 (GSK-3) inhibitors were developed to replace lithium chloride for use in psychiatric disorders. In addition, they were advocated as treatment for T2D since GSK-3 inhibition improves blood glucose handling...
June 2016: Cardiovascular Drugs and Therapy
Patrícia Ramos, Agostinho Santos, Edgar Pinto, Nair Rosas Pinto, Ricardo Mendes, Teresa Magalhães, Agostinho Almeida
The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder...
April 7, 2016: Journal of Trace Elements in Medicine and Biology
Celina S Liu, Myuri Ruthirakuhan, Sarah A Chau, Nathan Herrmann, André F Carvalho, Krista L Lanctôt
Agitation and aggression are common neuropsychiatric symptoms of Alzheimer's disease and are highly prevalent in people with dementia. When pharmacological intervention becomes necessary, current clinical practice guidelines recommend antipsychotics, cholinesterase inhibitors, and some antidepressants. However, those interventions have modest to low efficacy, and those with the highest demonstrated efficacy have significant safety concerns. As a result, current research is focusing on novel compounds that have different mechanisms of action and that may have a better balance of efficacy over safety...
2016: Current Alzheimer Research
Edward C Lauterbach
Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer's disease (AD) and the pre-motor stages of Parkinson's disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD...
2016: American Journal of Neurodegenerative Disease
Seong S Shim, Grace E Stutzmann
Although traumatic brain injury (TBI) has been a major public health concern for decades, the pathophysiological mechanism of TBI is not clearly understood, and an effective medical treatment of TBI is not available at present. Of particular concern is sustained TBI, which has a strong tendency to take a deteriorating neurodegenerative course into chronic traumatic encephalopathy (CTE) and dementia, including Alzheimer's disease. Tauopathy and beta amyloid (Aβ) plaques are known to be the key pathological markers of TBI, which contribute to the progressive deterioration associated with TBI such as CTE and Alzheimer's disease...
December 1, 2016: Journal of Neurotrauma
Orestes V Forlenza, Ivan Aprahamian, Vanessa J de Paula, Tomas Hajek
BACKGROUND: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer's disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. METHODS: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014...
2016: Current Alzheimer Research
Gerwyn Morris, Michael Berk
Alzheimer`s disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway...
2016: Current Alzheimer Research
J Gallinat, C Mulert, G Leicht
The generation of an electroencephalogram (EEG) provides a sensitive, non-invasive and inexpensive method for the investigation of brain function. This article critically reviews the significance of EEG examinations in clinical psychiatric practice and describes relevant applications and limitations. A summary of the basic principles of the production and interpretation of an EEG is followed by a survey of typical EEG patterns in healthy subjects and pathological alterations of EEG patterns. The importance of the EEG for the clinical diagnostics of Alzheimer's disease and acute delirium as well as the differentiation between psychiatric syndromes and non-convulsive status epilepticus is reviewed...
March 2016: Der Nervenarzt
Marielza Andrade Nunes, Natalia Mendes Schöwe, Karla Cristina Monteiro-Silva, Ticiana Baraldi-Tornisielo, Suzzanna Ingryd Gonçalves Souza, Janaina Balthazar, Marilia Silva Albuquerque, Ariadiny Lima Caetano, Tania Araujo Viel, Hudson Sousa Buck
No abstract text is available yet for this article.
2015: PloS One
Fábio B Mury, Weber C da Silva, Nádia R Barbosa, Camila T Mendes, Juliana S Bonini, Jorge Eduardo Souza Sarkis, Martin Cammarota, Ivan Izquierdo, Wagner F Gattaz, Emmanuel Dias-Neto
Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory...
October 2016: European Archives of Psychiatry and Clinical Neuroscience
Huntington Potter, Antoneta Granic, Julbert Caneus
Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (Aβ) peptide production underlie the universal development of Alzheimer's disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also arise among neurons and peripheral cells in both sporadic and familial AD and in mouse and cell models thereof, reinforcing the conclusion that AD and DS are two sides of the same coin. The demonstration that 90% of the neurodegeneration in AD can be attributed to the selective loss of aneuploid neurons generated over the course of the disease indicates that aneuploidy is an essential feature of the pathogenic pathway leading to the depletion of neuronal cell populations...
2016: Current Alzheimer Research
Marielza Andrade Nunes, Natalia Mendes Schöwe, Karla Cristina Monteiro-Silva, Ticiana Baraldi-Tornisielo, Suzzanna Ingryd Gonçalves Souza, Janaina Balthazar, Marilia Silva Albuquerque, Ariadiny Lima Caetano, Tania Araujo Viel, Hudson Sousa Buck
The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer's disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD...
2015: PloS One
Vanessa de Jesus De-Paula, Daniel Shikanai Kerr, Marília Palma Fabiano de Carvalho, Evelin Lisete Schaeffer, Leda Leme Talib, Wagner Farid Gattaz, Orestes Vicente Forlenza
BACKGROUND: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. OBJECTIVE: To investigate the effect of lithium on cytosolic phospholipase A₂ (PLA₂) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer's disease (AD)...
2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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