Long-Term Lithium Treatment Increases cPLA2 and iPLA2 Activity in Cultured Cortical and Hippocampal Neurons
| Autor: | Orestes Vicente Forlenza, Evelin L. Schaeffer, Leda Leme Talib, Wagner F. Gattaz, Daniel S. Kerr, Marília Palma Carvalho, Vanessa J. De-Paula |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
cPLA2 activity Lithium (medication) iPLA2 activity Pharmaceutical Science Hippocampus Hippocampal formation Neuroprotection Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound Phospholipase A2 lcsh:Organic chemistry Internal medicine Drug Discovery medicine Physical and Theoretical Chemistry biology Organic Chemistry Endocrinology medicine.anatomical_structure lithium neuronal cell culture chemistry Chemistry (miscellaneous) Cerebral cortex biology.protein Molecular Medicine Lithium chloride Neurotrophin medicine.drug |
| Zdroj: | Molecules, Vol 20, Iss 11, Pp 19878-19885 (2015) Molecules; Volume 20; Issue 11; Pages: 19878-19885 Molecules Volume 20 Issue 11 Pages 19878-19885 |
| ISSN: | 1420-3049 |
| Popis: | Background: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. Objective: To investigate the effect of lithium on cytosolic phospholipase A2 (PLA2) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer’s disease (AD). Methods: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA2 and two PLA2 subtypes: cytosolic calcium-dependent (cPLA2) and calcium-independent (iPLA2). Results: cPLA2 activity increased by 82% (0.02 mM p = 0.05) and 26% (0.2 mM p = 0.04) in cortical neurons and by 61% (0.2 mM p = 0.03) and 57% (2 mM p = 0.04) in hippocampal neurons. iPLA2 activity was increased by 7% (0.2 mM p = 0.04) and 13% (2 mM p = 0.05) in cortical neurons and by 141% (0.02 mM p = 0.0198) in hippocampal neurons. Conclusion: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA2. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA2 subtypes is tissue specific, i.e., iPLA2 in hippocampal neurons, and cPLA2 in cortical neurons. Because PLA2 activities are reported to be reduced in Alzheimer’s disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease. |
| Databáze: | OpenAIRE |
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