Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

Mendes, Camila T.; Mury, Fábio B.; Moreira, Eloisa De Sá; Alberto, Fernando; Forlenza, Orestes Vicente; Dias-Neto, Emmanuel; Gattaz, Wagner F.

doi:10.1007/s00406-008-0828-5

Cited by 96 publications

(59 citation statements)

References 31 publications

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“…After defining and experimentally validating the brain-related Pla2 set, we investigated their possible modulation by lithium. Therapeutic and even sub-therapeutic lithium concentrations have been shown to be capable of modulating Gsk3b mRNA [9] and protein [61,62], and it also seems to be capable of rescuing or attenuating longterm potentiation deficits due to GSK-3 dysfunction [63], improving learning and memory in rats [21,64] and reducing subsequent dementia rates in chronically treated elderly bipolar patients [30], which was further replicated in a large cohort of 4856 patients with a diagnosis of a manic or mixed episode or bipolar disorder [64]. Moreover, lithium treatment over 2 years reduced the conversion to AD in individuals with mild cognitive impairment [11,65].…”

Section: Discussionmentioning

confidence: 99%

“…Over the years, the mechanisms of action of lithium have been mainly evaluated from the perspective of its effects over the enzyme glycogen synthase kinase 3-beta (GSK3B) [7][8][9][10], as well as over neurotransmitters and G-proteincoupled second messenger systems [11,12]. However, some aspects of the therapeutic basis of lithium remain to be revealed.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

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Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Mury

Silva

Barbosa

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Mury

Silva

Barbosa

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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“…Являясь конкурентным антагонистом ионов Mg 2+ , литий оказывает прямое ингибирующее воздействие на Mg-АТФ-зависимую каталитическую активность GSK-3β in vitro и in vivo [15]. Кроме того, показано существование множества механизмов косвенного ингибирования лити-ем активности GSK-3β.…”

Section: молекулярные маршруты нейропротективных эффектов литияunclassified

Neurotrophic effects of lithium stimulate the reduction of ischemic and neurodegenerative brain damage

Пронин

Гоголева

Torshin

et al. 2016

Z. nevrol. psikhiatr. im. S.S. Korsakova

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ОБЗОРЫСоли лития уже более 60 лет используются в психиат-рической практике для лечения биполярных расстройств. В настоящее время основным медицинским показанием для применения лития является лечение биполярного аф-фективного расстройства, также соли лития применяются в качестве препарата второго ряда для лечения депрессии [1,2]. Кроме того, препараты лития имеют антисуици-дальные свойства [3]. В психиатрии литий (прежде всего в форме карбоната лития) применяется в дозах, исчисляе-мых сотнями мг в расчете на элементный литий (чему со-ответствует 2-10 г карбоната лития). Такие дозы приво-дят к проявлению тяжелых нежелательных эффектов во время терапии (патология почек, тератогенез). Уже более 60 лет высокие дозы лития (сотни мг в расчете на элементный литий) используются для лечения биполярного аффективного расстройства. Проведенные за последние 20 лет экспериментальные исследования показывают, что нейропротективные и нейротрофические эффекты лития в гораздо меньших дозировках (сотни мкг) имеют существенный потенциал в неврологии -для профилактики и лечения ишемических повреждений и дегенеративных заболеваний ЦНС. Ингибирование гликоген-синтетазы-киназы-3 и индукция мозгового нейротрофического фактора являются основными механизмами действия лития. Также посредством ингибирования NMDA-рецепторов литий регулирует кальциевый гомеостаз и подавляет кальций-зависимую активацию апоптоза. С помощью этих и других молекулярных механизмов препараты лития защищают нервные клетки в экспериментальных моделях инсульта и нейродегенеративных заболеваний, что способствует достоверному снижению неврологического дефицита. Ключевые слова: мозговой нейротрофический фактор (BDNF), гликоген-синтетаза-киназа-3 (GSK-3), литий-α, нейродегенеративные заболевания, ишемия головного мозга.For over 60 years, high doses of lithium (hundreds of milligrams of elemental lithium) have being used to treat bipolar disorder. However, only during the past 20 years the relevant basic and clinical studies have shown that neuroprotective and neurotrophic effects of lithium are possible in much smaller doses (hundreds of micrograms of elemental lithium). These data indicate a significant potential for the clinical applications of lithium-based drugs in modern neurology for the purposes of prevention and treatment of neurodegenerative and ischemic pathologies. Pharmacological and molecular biology studies indicate that the inhibition of glycogen synthase kinase-syntentase-3 (GSK-3) and induction of brain-derived neurotrophic factors are the main mechanisms of neurotropic actions of lithium. Also, by inhibiting the NMDA receptors, lithium regulates the calcium homeostasis and inhibits the activation of calcium-dependent apoptosis. These and other molecular mechanisms of lithium action protect neurons from ischemia and neurodegeneration thus contributing to a significant reduction of neurological deficit in various models of stroke and neurodegenerative diseases.

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“…It is well known that the risk of recurrence of affective episodes increases with the number of prior affective episodes and some evidence further suggests that the rate of dementia also increases with the number of affective episodes as the illness goes on [14]. The pathogenetic mechanisms are unknown but a key hypothesis has emerged in relation to glycogen synthase kinase 3B, which is a key enzyme in the metabolism of amyloid precursor protein and in the phosphorylation of the tau protein involved in the pathogenesis of Alzheimer's disease [15,16]. Preliminary new data suggest that glycogen synthase kinase 3B activity is increased in patients with mild cognitive impairment and in Alzheimer's disease [17] and also in patients with late-life depression [18].…”

Section: Bd Dementia and Lithiummentioning

confidence: 99%

“…Preliminary new data suggest that glycogen synthase kinase 3B activity is increased in patients with mild cognitive impairment and in Alzheimer's disease [17] and also in patients with late-life depression [18]. Interestingly, among the many effects of lithium, it inhibits glycogen synthase kinase 3 [15,16]. Accordingly, findings from large register-based studies suggest that continued treatment with lithium reduces the risk of developing dementia in the long run among patients with BDs [19,20].…”

Section: Bd Dementia and Lithiummentioning

confidence: 99%

Bipolar Disorder in the Elderly

et al. 2011

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Over 1200 participants from a wide array of psychogeriatric disciplines attended the 15th world congress of the International Psychogeriatric Association (IPA) in The Netherlands. In previous years, the meetings and activities of the IPA were strongly focused on research restricted to diagnosis and care of individuals with dementia. In recent years, there has been a shift of attention towards other psychiatric disorders in the elderly such as schizophrenia, substance abuse and bipolar disorder, which were for a long time nearly invisible in the scientific literature. The symposium venue was located in The Hague, a typical Dutch town not far from the coastline and home to several famous international institutions in the field of peace and justice. This successful meeting with the theme ‘Reinventing Aging through Innovation, Care, Research, Technology’ was co-chaired by Anne Margriet Pot (Professor of Geropsychology, Amsterdam, The Netherlands) and Frans Verhey (Professor of Neuropsychiatry, Maastricht, The Netherlands). A special symposium on ‘Bipolar Disorder in the Elderly’ also took place during the 4-day meeting. This symposium was organized by The Netherlands Psychiatric Association, Faculty of Old Age Psychiatry and is an example of a neglected topic in geriatric mental health and represents the important diverse mental disorders that a large proportion of older adults and their families can experience. The symposium was co-chaired by Max Stek, Professor of Old Age Psychiatry and Chair of the Dutch Faculty of Old Age from The Netherlands and Martha Sajatovic from the USA. Presenting faculty were Ralph Kupka and Annemiek Dols from The Netherlands and Lars Kessing from Denmark.

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Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

Cited by 96 publications

References 31 publications

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Neurotrophic effects of lithium stimulate the reduction of ischemic and neurodegenerative brain damage

Bipolar Disorder in the Elderly

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