Acute and chronic lithium treatment increases Wnt/beta-catenin transcripts in cortical and hippocampal tissue at therapeutic concentrations in mice

Author(s)

De-Paula, Vanessa J. ^{[1, 2, 3]} ; dos Santos, Carla Cristine C. ^[4] ; Luque, Maria Carolina A. ^{[5, 4]} ; Ali, Taccyana M. ^{[5, 4]} ; Kalil, Jorge E. ^{[2, 5, 6]} ; Forlenza, Orestes V. ^[6] ; Cunha-Neto, Edecio ^{[5, 6, 4]}

Affiliation

^[1] Univ Sao Paulo, Dept & Inst Psiquiatria, Hosp Clin HCFMUSP, Lab Psicobiol LIM23, Fac Med, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept & Inst Psiquiatria, Hosp Clin HCFMUSP, Lab Neurociencias LIM27, Fac Med, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci, Fac Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Div Imunol & Clin Alergia, Lab Imunol Clin & Alergia LIM60, Fac Med, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Fac Med, Inst Coracao InCor, Lab Imunol, Sao Paulo, SP - Brazil

^[6] Inst Invest Imunol iii INCT, Sao Paulo - Brazil

• Document type: Journal article
• Source: METABOLIC BRAIN DISEASE; v. 36, n. 1 NOV 2020.
• Web of Science Citations: 0

Abstract

Lithium activates Wnt/beta-catenin signaling leading to stabilization of free cytosolic beta-catenin. The aim of the present study is to evaluate the in vivo effect of acute and chronic lithium treatment on the expression of beta-catenin target genes, addressing its transcripts HIG2, Bcl-xL, Cyclin D1, c-myc, in cortical and hippocampal tissue from adult mice. Lithium doses were established to yield therapeutic working concentrations. In acute treatment, mice received a 300 mu L of a 350 mg/kg solution of LiCl by gavage, and were euthanized after 2 h, 6 h and 12 h. To determine the effect of chronic treatment, animals were continuously fed either with chow supplemented with 2 g/kg Li2CO3, or regular chow (controls), being euthanized after 30 days. All animals had access to drinking water and 0.9% saline ad libitum. After acute and chronic treatments samples of peripheral blood were obtained from the tail vein for each animal, and serum concentrations of lithium were determined. All transcripts were up-regulated in cortical and hippocampal tissues of lithium-treated mice, both under acute and chronic treatments. There was a positive correlation between serum lithium concentrations and the increment in the expression of all transcripts. This effect was observed in all time points of the acute treatment (i.e., 2, 6 and 12 hours) and also after 30 days. We conclude that Wnt/beta-catenin transcriptional response (HIG2, Bcl-xL, Cyclin D1 and c-myc) is up-regulated in the mouse brain in response to acute and chronic lithium treatment at therapeutic concentrations. (AU)

• FAPESP's process: 14/50890-5 - INCT of Investigation in Immunology
• Grantee: Jorge Elias Kalil Filho
• 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: 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: 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