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Neuroprotective and neurotrophic effects of long term lithium treatment in mouse brain

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Abstract

Since the worldwide approval of lithium therapy in 1970, lithium has been used for its anti-manic, antidepressant, and anti-suicidal effects. The last decade has witnessed the following discoveries about its neuroprotective and neurotrophic properties, yet the therapeutic mechanisms at the cellular level remain not-fully defined. We have undertaken the present study to determine if chronic lithium treatment, at therapeutically relevant concentrations, exerts neurotrophic/neuroprotective effects in the mouse brain in vivo. For this purpose, 10 months aged mice were fed for 3 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.4 and 0.8 mM, respectively. The evaluation of lipid peroxidation level and the activities of catalase, superoxide-dismutase and glutathione-peroxidase showed that chronic Li administration, at therapeutic doses doesn’t induce oxidative stress in brain tissue. No changes in the expression levels of molecular chaperones, namely, the HSP70, and HSP90 heat shock proteins and the GRP94 glucose-regulated protein were detected. Moreover, this treatment has caused (1) an increase in the relative brain weight (2) a delay in the age induced cerebral glucose impairment (3) an enhancement of the neurogenesis in hippocampus and enthorinal cortex highlighted by silver impregnation. Under these experimental conditions, no modifications were observed in expression levels of GSK3 and of its downstream target β-catenin proteins. These results suggested that chronic Li administration, at therapeutic doses, has a neuroprotective/neurotrophic properties and its therapeutic mechanism doesn’t implicate GSK3 inactivation.

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Authors and Affiliations

  1. Laboratoire d’Ecophysiologie Animale, Faculté des Sciences de Sfax, PB 802, 3018, Sfax, Tunisia

    Nciri Riadh, Mohamed Salah Allagui, Ezzedine Bourogaa & Abdelfattah Elfeki

  2. Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine Toulouse Purpan, Toulouse, France

    Nciri Riadh, Mohamed Salah Allagui, Christian Vincent & Françoise Croute

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  1. Nciri Riadh
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  2. Mohamed Salah Allagui
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  3. Ezzedine Bourogaa
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  4. Christian Vincent
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  5. Françoise Croute
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  6. Abdelfattah Elfeki
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Correspondence to Nciri Riadh.

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Riadh Nciri and Mohamed Salah Allagui have equally contributed to this work.

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Riadh, N., Allagui, M.S., Bourogaa, E. et al. Neuroprotective and neurotrophic effects of long term lithium treatment in mouse brain. Biometals 24, 747–757 (2011). https://doi.org/10.1007/s10534-011-9433-6

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  • DOI: https://doi.org/10.1007/s10534-011-9433-6

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