Neuroprotective and neurotrophic effects of long term lithium treatment in mouse brain
| Autor: | Christian Vincent, Françoise Croute, Mohamed Salah Allagui, Nciri Riadh, Ezzedine Bourogaa, Abdelfattah Elfeki |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Lithium (medication) Mice Inbred Strains Lithium medicine.disease_cause Neuroprotection General Biochemistry Genetics and Molecular Biology Antioxidants Biomaterials Lipid peroxidation chemistry.chemical_compound Glycogen Synthase Kinase 3 Mice In vivo Internal medicine medicine Animals Glycogen Synthase Kinase 3 beta biology Dose-Response Relationship Drug Brain-Derived Neurotrophic Factor Lithium carbonate Metals and Alloys Brain Hsp70 Endocrinology Neuroprotective Agents chemistry biology.protein Lipid Peroxidation General Agricultural and Biological Sciences Oxidative stress medicine.drug Neurotrophin |
| Zdroj: | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 24(4) |
| ISSN: | 1572-8773 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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