Neurotrophic signaling cascades are major long-term targets for lithium: clinical implications

Yuan, Peixiong; Gould, Todd D.; Gray, N. A. B.; Bachmann, Rosilla; Schloesser, Robert J.; Lan, Martin; Du, Jing; Moore, Gregory J.; Manji, Husseini K.

doi:10.1016/j.cnr.2004.09.006

Cited by 9 publications

(10 citation statements)

References 137 publications

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“…In the recent studies, lithium has been shown to exert neuroprotective effects against various stimuli both in vitro and in vivo (Li et al 2002;Yuan et al 2004;Aghdam et al 2007). Further, lithium has also been shown to inhibit cell death, DNA fragmentation and lipid peroxidation (Tandon et al 1998;Shao et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Potential of lithium to reduce aluminium-induced cytotoxic effects in rat brain

2009

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The present study was aimed to explore the potential of an antidepressant drug lithium (Li) in reducing aluminium (Al) induced neurotoxicity. To carry out the investigations, Al was administered orally (100 mg AlCl(3)/Kg b wt/day) whereas, Li was administered through diet (1.1 g Li(2)CO(3)/Kg diet, daily) for a total duration of 2 months. Al treatment resulted in a significant increase in the activity of enzyme nitric oxide synthase and the levels of L-citrulline which, however, were decreased appreciably following lithium supplementation. Al treatment also revealed an increase in DNA fragmentation as evidenced by an increase in number of comets. Interestingly, Li supplementation to Al treated rats reduced the damage inflicted on DNA by Al. Ultrastructural studies revealed an increase in chromatin condensation with discontinuity in nuclear membrane in both the cerebrum and cerebellum of Al treated rats which showed improvement following Li supplementation. Alterations in the structure of synapse and mitochondrial swelling were also seen. The present study shows the potential of Li in containing the damage inflicted by Al on rat brain.

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Section: Introductionmentioning

confidence: 99%

Potential of lithium to reduce aluminium-induced cytotoxic effects in rat brain

2009

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“…Despite its long-standing clinical use and intensive investigation, there has been no consensus on the molecular mechanisms underlying the therapeutic function of lithium. Experiments support multiple targets of this drug regulating the expression of numerous molecules and enzymes involved in neuroplasticity, neuroprotection, and mitochondrial function including Bcl-2, GSK-3, and the ERK/MAP kinase pathway (Gould et al, 2002;Yuan et al, 2004;Wada et al, 2005).…”

Section: Introductionmentioning

confidence: 94%

“…Recent data have suggested that mood disorders are associated with a reduction in regional central nervous system volume, due to the atrophy and loss of neurons and glial cells (Gould et al, 2002;Yuan et al, 2004;Wada et al, 2005). These structural alterations do not resemble those of classical neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

“…It increased the level of antiapoptotic Bcl-2 protein (Chen and Chuang, 1999;, or reduced the level of proapoptotic proteins: p53 (Chen and Chuang, 1999;Lu et al, 1999), Bax protein (Chen and Chuang, 1999;Ghribi et al, 2002), or activation of caspase-3 (Ghribi et al, 2002;Mora et al, 2002). Not only did lithium suppress the induction of apoptosis, it also exerted neurotrophic effects (Yuan et al, 2004;Wada et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…The protective role of lithium has been well documented in vitro and in vivo (Yuan et al, 2004;Wada et al, 2005). However, its beneficial effect on glial cells (or cells of glial origin) needs to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Lithium increases expression of p21WAF/Cip1 and survivin in human glioblastoma cells

Karlović¹,

Jakopec

Dubravčić

et al. 2006

Cell Biol Toxicol

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Lithium is the most widely prescribed mood stabilizer, but the precise molecular mechanisms underlying its therapeutic function are not yet fully elucidated. Recent preclinical and clinical evidence indicates its neuroprotective and neurotrophic effects. As a tight coupling of function and metabolism in the central nervous system between glial cells and neurons has recently been detected, lithium's effect on glial cells may participate also in the total beneficial effects of this drug. The aim of the present study was to analyze molecular mechanisms induced in human glioblastoma A1235 cells by the treatment with lithium, especially its influence on the expression of apoptosis-related genes. Lower levels of lithium (0.5 mmol/L and 2 mmol/L) did not cause any cytotoxicity or changes in the cell cycle phase distribution following 72 h incubation. However, a higher dose (20 mmol/L) was cytostatic for glioblastoma cells, and caused accumulation of cells in G(2)/M phase of the cell cycle. The treatment with lithium did not alter the levels of Bcl-2 or procaspase-3 and did not cleave PARP, but increased the levels of p21(WAF/Cip1) and survivin. Thus, increased expression of p21(WAF/Cip1) (a protein with antiapoptotic function), and survivin (a protein that supports the growth of cells by suppression of apoptosis and promotion of cell proliferation) may be the early events in the long-term cell response to lithium that are involved in the beneficial effects of this drug.

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Neurobiology and Pharmacotherapy of Bipolar Disorder

Belmaker

Agam

Lenox

2007

Handbook of Contemporary Neuropharmacology

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Given the complexity of the interaction of the physiological, genetic and environmental factors driving the clinical expression of bipolar disorder phenotypes, its neurobiology is yet to be unraveled and avenues to new pharmacotherapies are just beginning to be explored. The present chapter describes the latest findings from studies of the mechanism of action of our most effective treatments, i.e., lithium and anticonvulsants, as well as ongoing multidisciplinary research in this field utilizing not only genetic, neuroimaging, and peripheral biological markers in patient populations but also postmortem neuroanatomical and neurochemical approaches. The data to‐date do not provide a comprehensive description of the pathophysiology of bipolar disorder or the mechanisms for mood‐stabilization. Enhanced understanding of the long‐term prophylactic action of drugs like lithium in the brain and current advances in the combined use of neuroimaging and genetics will lead to important insights into the neurobiology of the disease and to a rational basis for the development of the novel antibipolar drugs of the future.

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Neurotrophic signaling cascades are major long-term targets for lithium: clinical implications

Cited by 9 publications

References 137 publications

Potential of lithium to reduce aluminium-induced cytotoxic effects in rat brain

Potential of lithium to reduce aluminium-induced cytotoxic effects in rat brain

Lithium increases expression of p21WAF/Cip1 and survivin in human glioblastoma cells

Neurobiology and Pharmacotherapy of Bipolar Disorder

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