Effects of lithium on the expression of the enzymes activity phospholipase A2 and glycogen synthase kinase 3beta and its relationship with the phosphorylation state of tau protein

Author(s)

Vanessa de Jesus Rodrigues de Paula

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2015-08-11

Examining board members

Orestes Vicente Forlenza; Tania Corrêa de Toledo Ferraz Alves; Homero Pinto Vallada Filho; Silvio Marques Zanata

• Advisor: Orestes Vicente Forlenza

Abstract

The present study compared the effect of lithium chronic treatment with subtherapeutic doses (0.02mM and 0.2mM) and therapeutic dose (2mM) in primary cortical and hippocampal neurons cell culture. This samples were analyzed and compared with the control group (no treatment). The study\'s goal was: 1) to evaluate in these Cell Culture a different activity kinases (PKA, CaMKII, AKT and GSK3beta), different phosphorylation site of the Tau (199, 205, 214, 396, C-terminal and Six isoforms) and PLA2 inhibition; 2) To investigate how signaling pathways involved in modulation of tau phosphorylation from the inhibition of PLA2 in primary cultures of neurons; 3) analyze an expression of neurotrophic factors (BDNF) and cytokines (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFNy TNFalfa 4) to evaluate gene expression via microarray with different doses of lithium treatment. Our results suggest a dissociation effects on cortical and hippocampal neurons cell culture. Lithium increased the enzyme activity of iPLA2 and cPLA2, in both cortical and hippocampal neurons. The GSK3beta the activity was inhibited by chronic treatment with lithium in hippocampal neurons and presented contrary effect on cortical neurons. We observe not statistics significance on tau protein. The treatment at subtherapeutic and therapeutic doses increased the secretion of pro and anti-inflammatory cytokines both in cortical and hippocampal neurons (AU)

• FAPESP's process: 11/19892-3 - Effects of lithium on the expression and activity of the enzymes Phospholipase A2 and glycogen synthase kinase 3B and its relation to the phosphorylation state of Tau protein
• Grantee: Vanessa de Jesus Rodrigues de Paula
• Support Opportunities: Scholarships in Brazil - Doctorate