Lithium Chloride Reinforces the Regeneration-Promoting Effect of Chondroitinase ABC on Rubrospinal Neurons after Spinal Cord Injury

Yick, Leung-Wah; So, Kwok-Fai; Cheung, Pik-To; Wu, Wutian

doi:10.1089/neu.2004.21.932

Cited by 29 publications

(23 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, a dual effect of LiCl in cell survival and axon growth is likely to be responsible for these results. Indeed, a single application of LiCl after spinal cord lesion does not promote the regeneration of rubrospinal axons (Yick et al 2004), and the over-expression of Bcl-2 does not stimulate axon regeneration per se in several lesion models (Chen and Tonegawa 1998;Chierzi et al 1999;Inoue et al 2002;Sole et al 2004). In contrast, LiCl has recently been used after spinal cord lesion (Dill et al 2008), and the results contrast with those reported by Alabed and co-workers (Alabed et al 2007; Society for Neuroscience) with respect to the inhibition of GSK3b.…”

Section: Discussionmentioning

confidence: 90%

“…The GSK3b-mediated inhibition of axon regeneration of lesioned neurons has been studied mainly through the use of pharmacological treatments with LiCl. Indeed, LiCl treatment combined with chondroitinase ABC (Yick et al 2004) promotes axon regeneration of ganglion cells in the retina (Huang et al 2003) and rubrospinal tract. These effects correlate with increased Bcl-2 expression and GSK3b inhibition (Yick et al 2004;Dill et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, LiCl treatment combined with chondroitinase ABC (Yick et al 2004) promotes axon regeneration of ganglion cells in the retina (Huang et al 2003) and rubrospinal tract. These effects correlate with increased Bcl-2 expression and GSK3b inhibition (Yick et al 2004;Dill et al 2008). Thus, a dual effect of LiCl in cell survival and axon growth is likely to be responsible for these results.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Seira

Gavı́n

Gil

et al. 2010

Journal of Neurochemistry

View full text Add to dashboard Cite

J. Neurochem. (2010) 113, 1644–1658. Abstract Lesioned axons do not regenerate in the adult mammalian CNS, owing to the over‐expression of inhibitory molecules such as myelin‐derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin‐associated inhibition, blockage with NEP1–40, receptor bodies or IN‐1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin‐associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3β (GSK3β) and extracellular‐related kinase (ERK) 1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3β and ERK1/2 activities facilitates regeneration after myelin‐directed inhibition in two models: (i) cerebellar granule cells and (ii) lesioned entorhino‐hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3β inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Finally, these regenerative effects were corroborated in the lesioned entorhino‐hippocampal pathway in NgR1−/− mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Seira

Gavı́n

Gil

et al. 2010

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…This correlated with decreases in eIF-2B, suggesting trauma-induced activation of GSK-3b may lead to alterations in protein synthesis. In addition, in adult rats receiving a unilateral hemisection at the seventh cervical spinal cord segment, phosphoSer9-GSK-3b was increased by administration of lithium chloride, a GSK regulator with neuroprotective properties (35). The inhibition of GSK by lithium enhanced the ability of chondroitinase ABC to promote regeneration of axotomized rubrospinal tract neurons.…”

Section: Gsk-3mentioning

confidence: 98%

Protein kinase signaling cascades in CNS trauma

Neary

2005

IUBMB Life (International Union of Biochemistry and Molecular B

View full text Add to dashboard Cite

SummaryAdvances in our understanding of the signaling pathways and cellular functions regulated by protein kinase cascades have paved the way to study their role in the response of brain and spinal cord to traumatic injury. Mechanical forces imparted by trauma stimulate mitogen-activated protein kinases and protein kinase B/Akt as well as cause changes in the state of phosphorylation of glycogen synthase kinase-3b. Extracellular ATP released by mechanical strain stimulates P2 purinergic receptors that are coupled to these protein kinase signaling pathways. These kinases regulate gene expression, cell survival, proliferation, differentiation, growth arrest, and apoptosis, thereby affecting cell fate, repair and plasticity after trauma. Elucidation of the molecular responses of protein kinase cascades to mechanical strain and the genes regulated by these signaling pathways may lead to therapeutic opportunities to minimize losses in motor skills and cognitive function caused by trauma to the central nervous system. IUBMB Life, 57: 711 -718, 2005

show abstract

“…На модели крыс с повреждени-ем спинного мозга, вызванным односторонней гемисек-цией, при комбинированном лечении препаратами лития с хондроитиназой был достигнут синергичный эффект. Отмечены увеличение регенерации аксонов в руброспи-нальном тракте и улучшение движения передних конеч-ностей [69]. Данный эффект терапии осуществлялся за счет увеличения секреции BDNF [70], который усиливает клеточное деление и дифференцировку клеток-предше-ственников нейронов, наряду с уменьшением активации микроглии и макрофагов [71].…”

Section: другие направления использования лития в медицинеunclassified

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

View full text Add to dashboard Cite

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.

show abstract

Lithium Chloride Reinforces the Regeneration-Promoting Effect of Chondroitinase ABC on Rubrospinal Neurons after Spinal Cord Injury

Abstract: CitationJournal

Cited by 29 publications

References 46 publications

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Protein kinase signaling cascades in CNS trauma

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

Contact Info

Product

Resources

About