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European Archives of Psychiatry and Clinical Neuroscience

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01.02.2009 | ORIGINAL PAPER

Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

verfasst von: Camila Teixeira Mendes, Fábio Borges Mury, Eloísa de Sá Moreira, Fernando Lopes Alberto, Orestes Vicente Forlenza, Emmanuel Dias-Neto, Wagner Farid Gattaz

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 1/2009

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Abstract

Background

There is evidence of increased systemic expression of active GSK3B in Alzheimer’s disease patients, which apparently is associated with the formation of senile plaques and neurofibrillary tangles. Due to its central role in the pathogenesis of AD, GSK3B is currently a promising target of the pharmaceutical industry. Whilst trials with specific GSK inhibitors in AD are under way, major attention has been focused on the neuroprotective effects of lithium. Whereas the direct and indirect inhibitory effects of lithium over GSK3 activity have been documented by several groups, its effects over Gsk3 transcription have not yet been addressed.

Methods

We used quantitative PCR to evaluate the transcriptional regulation of Gsk3a and Gsk3b in lithium-treated primary cultures of rat cortical and hippocampal neurons.

Results

We found a significant and dose-dependent reduction in the expression of Gsk3b, which was specific to hippocampal cells. This same effect was further confirmed in vivo by measuring Gsk3 expression in different brain regions and in peripheral leukocytes of adult rats treated with lithium.

Conclusion

Our studies show that LiCl can modulate Gsk3b transcription in vitro and in vivo. This observation suggest new regulatory effects of lithium over Gsk3b, contributing to the better understanding of its mechanisms of action, offering a new and complementary explanation for Gsk3b modulation and reinforcing its potential for the inhibition of key pathological pathways in Alzheimer’s disease.

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Titel: Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease
verfasst von: Camila Teixeira Mendes
Fábio Borges Mury
Eloísa de Sá Moreira
Fernando Lopes Alberto
Orestes Vicente Forlenza
Emmanuel Dias-Neto
Wagner Farid Gattaz
Publikationsdatum: 01.02.2009
Verlag: Steinkopff-Verlag
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 1/2009
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-008-0828-5

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Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

Abstract

Background

Methods

Results

Conclusion

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Abstract

Background

Methods

Results

Conclusion

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