Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia

Yan, Xinfeng; Hou, Hailong; Wu, Lin-Min; Liu, Ji; Zhou, Jiang‐Ning

doi:10.1016/j.neuropharm.2007.06.020

Cited by 112 publications

(81 citation statements)

References 45 publications

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“…However, in this study, the proportion of neuronal and astrocyte differentiation was not different between the lithium and vehicle groups. This is consistent with one report on lithium effects on transient global cerebral ischemia in adult rats (Yan et al, 2007a), but different from another report where lithium increased neurogenesis and decreased astrogliogenesis (Kim et al, 2004). The reason for this discrepancy may depend on differences in the age of the animals, the timing of BrdU injection, and the type or degree of injury.…”

Section: Discussionsupporting

confidence: 86%

“…A number of studies indicate that lithium appears to act on proliferation, but the signal transduction pathway responsible for this effect has not been identified (Su et al, 2007;Yan et al, 2007a). It has been reported that lithium stimulates progenitor proliferation in cultured brain neurons (Hashimoto et al, 2003), shifts the phenotype from predominantly astrocytic to neuronal (Kim et al, 2004), and inhibits apoptosis of mouse NSPCs (Shimomura et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Lithium-Mediated Long-Term Neuroprotection in Neonatal Rat Hypoxia–Ischemia is Associated with Antiinflammatory Effects and Enhanced Proliferation and Survival of Neural Stem/Progenitor Cells

et al. 2011

J Cereb Blood Flow Metab

105

112

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The aim of this study was to evaluate the long-term effects of lithium treatment on neonatal hypoxicischemic brain injury, inflammation, and neural stem/progenitor cell (NSPC) proliferation and survival. Nine-day-old male rats were subjected to unilateral hypoxia-ischemia (HI) and 2 mmol/kg lithium chloride was injected intraperitoneally immediately after the insult. Additional lithium injections, 1 mmol/kg, were administered at 24-hour intervals for 7 days. Animals were killed 6, 24, 72 hours, or 7 weeks after HI. Lithium reduced total tissue loss by 69%, from 89.4 ± 14.6 mm 3 in controls (n = 15) to 27.6 ± 6.2 mm 3 in lithium-treated animals (n = 14) 7 weeks after HI (P < 0.001). Microglia activation was inhibited by lithium treatment, as judged by Iba-1 and galectin-3 immunostaining, and reduced interleukin-1b and CCL2 levels. Lithium increased progenitor, rather than stem cell, proliferation in both nonischemic and ischemic brains, as judged by 5-bromo-2-deoxyuridine labeling 24 and 72 hours as well as by phospho-histone H3 and brain lipid-binding protein labeling 7 weeks after HI. Lithium treatment also promoted survival of newborn NSPCs, without altering the relative levels of neuronal and astroglial differentiation. In summary, lithium conferred impressive, morphological long-term protection against neonatal HI, at least partly by inhibiting inflammation and promoting NSPC proliferation and survival.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Lithium-Mediated Long-Term Neuroprotection in Neonatal Rat Hypoxia–Ischemia is Associated with Antiinflammatory Effects and Enhanced Proliferation and Survival of Neural Stem/Progenitor Cells

et al. 2011

J Cereb Blood Flow Metab

105

112

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“…13 Further pathways include prevention of excitotoxicity, upregulation of antiapoptotic Bcl-2 and brain-derived-neurotrophic factor (BDNF) as well as induction of prosurvival phosphatidylinositol 3-kinase (PI3K)/Akt, all of which promote neuronal survival. [14][15][16][17][18] Moreover, lithium stimulates endogenous neurogenesis and promotes neuronal differentiation under physiological conditions 12,[19][20][21][22][23] and in models of global cerebral ischemia. 12,21 Neuronal differentiation is critically controlled by the RE1-silencing transcription factor (REST, also known as NRSF).…”

Section: Introductionmentioning

confidence: 99%

Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3β inhibition-independent pathways

Doeppner

Kaltwasser

Sánchez-Mendoza

et al. 2016

J Cereb Blood Flow Metab

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Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3b inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry. Lithium-induced neuroprotection persisted throughout the observation period of 56 days and was associated with enhanced neurological recovery. Poststroke angioneurogenesis and axonal plasticity were also enhanced by lithium. On the molecular level, lithium increased miR-124 expression, reduced RE1-silencing transcription factor abundance, and decreased protein deubiquitination in cultivated cortical neurons exposed to oxygen-glucose deprivation and in brains of mice exposed to cerebral ischemia. Notably, this effect was not mimicked by pharmacological GSK3b inhibition. This study for the first time provides efficacy data for lithium in the postacute ischemic phase, reporting a novel mechanism of action, i.e. increased miR-124 expression facilitating REST degradation by which lithium promotes postischemic neuroplasticity and angiogenesis.

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“…Animal studies suggest that lithium improves memory deficits induced by neuropathological insults [18,19] and indicate its potential use as a therapeutic agent in cognitive decline [20]. Nocjar et al [21] found that a 4-week lithium treatment significantly improved memory recognition and learning in rats and promoted hippocampal synaptic plasticity.…”

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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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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Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia

Cited by 112 publications

References 45 publications

Lithium-Mediated Long-Term Neuroprotection in Neonatal Rat Hypoxia–Ischemia is Associated with Antiinflammatory Effects and Enhanced Proliferation and Survival of Neural Stem/Progenitor Cells

Lithium-Mediated Long-Term Neuroprotection in Neonatal Rat Hypoxia–Ischemia is Associated with Antiinflammatory Effects and Enhanced Proliferation and Survival of Neural Stem/Progenitor Cells

Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3β inhibition-independent pathways

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

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