Long-Term Lithium Treatment Increases cPLA₂ and iPLA₂ Activity in Cultured Cortical and Hippocampal Neurons

• Published in: Molecules (Basel, Switzerland) Switzerland), 2015-11, Vol.20 (11), p.19878-19885
• Main Authors: De-Paula, Vanessa de Jesus, Kerr, Daniel Shikanai, de Carvalho, Marília Palma Fabiano, Schaeffer, Evelin Lisete, Talib, Leda Leme, Gattaz, Wagner Farid, Forlenza, Orestes Vicente
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Autophagy; Bipolar disorder; Cell culture; Cell Survival - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chloride; cPLA2 activity; Dementia; Disease prevention; Enzymes; Female; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Homeostasis; iPLA2 activity; Kinases; Lithium; Lithium - pharmacology; Metabolism; neuronal cell culture; Neurons - drug effects; Neurons - metabolism; Phospholipases A2 - metabolism; Pregnancy; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Rats; Signal transduction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201119663

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. 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). 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). 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. 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.