Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations

Author(s)

De-Paula, Vanessa J. ; Gattaz, Wagner F. ; Forlenza, Orestes V.

• Document type: Journal article
• Source: BIPOLAR DISORDERS; v. 18, n. 8, p. 692-695, DEC 2016.
• Web of Science Citations: 6

Abstract

Objectives: The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion. Methods: Primary cultures of cortical and hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM) and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical and hippocampal cell culture. Results: Lithium treatment increased the intracellular protein expression of cortical neurons (10% at 0.02 mM) and hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively). Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM, respectively and in hippocampal neurons increased 44% at 0.02 mM. Conclusion: The present study indicates that chronic, low-dose lithium treatment -up-regulates BDNF production in primary neuronal cell culture. (AU)

• FAPESP's process: 09/52825-8 - Neurobiology of Alzheimer's disease: risk markers, prognosis and therapeutic response
• Grantee: Wagner Farid Gattaz
• Support Opportunities: Research Projects - Thematic Grants
• 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
• FAPESP's process: 16/01302-9 - Direct and indirect pathways of glycogen synthase kinase 3B inhibition by lithium in culture of neurons
• Grantee: Vanessa de Jesus Rodrigues de Paula
• Support Opportunities: Scholarships in Brazil - Post-Doctoral