Lithium effect on micro RNA regulation of gene expression on an Alzheimer's Disease model by beta-amyloid induced neurotoxicity in neuronal primary cell culture

• Grant number: 13/01352-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2013
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Daniel Shikanai Kerr
• Grantee: Daniel Shikanai Kerr
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Emmanuel Dias-Neto ; Helena Paula Brentani ; Orestes Vicente Forlenza ; Vanessa de Jesus Rodrigues de Paula ; Wagner Farid Gattaz

Abstract

It is estimated that there are 35 million people with Alzheimer's Disease (AD), this number could increase to 120 million by 2050. It is estimated that annual costs with dementia are near 600 billion dollars and increasing. Although the physiopathological characteristics are well known, the mechanisms behind its genesis are not, also there is no effective treatment. Lithium has been suggested as an alternative for AD prevention, or slowing the disease progression. Lithium has neurotrophic and neuroprotective effects and it has been studied because of its action on both pro and anti apoptotic proteins. Here we are going to evaluate the effect of lithium on micro RNA (miRNA) delimited gene expression networks in neuronal primary culture, treated with ²-amyloid (BA). miRNAs are RNA molecules with aproximately 20 bases, which modulate expression in a post-transcriptional level. Each miRNA can modulate several proteins and a protein may be regulated by several miRNAs. So, each miRNA delimits a gene network which it can regulate. The treatment of primary neuronal cell culture with BA is a well-known model of in vitro neurodegeneration, widely used in AD research. Furthermore, it has been shown miRNA expression changes in this model. miRNA modulation by lithium was seen in other models. Our aims are: to identify miRNAs with altered expression in our model, characterize the gene expression networks delimited by those miRNAs and lastly, evaluate the expression of key genes in said networks. This approach might help characterize important genes in both our neurodegeneration model and in lithium response. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE-PAULA, VANESSA J.; KERR, DANIEL S.; SCOLA, GUSTAVO; GATTAZ, WAGNER F.; FORLENZA, ORESTES V.. Lithium Distinctly Modulates the Secretion of Pro- and Anti-Inflammatory Interleukins in Co-Cultures of Neurons and Glial Cells at Therapeutic and Sub-Therapeutic Concentrations. Current Alzheimer Research, v. 13, n. 8, p. 848-852, 2016. (13/01352-8, 11/19892-3, 02/13633-7)

POLHO, G. B.; DE-PAULA, V. J.; CARDILLO, G.; DOS SANTOS, B.; KERR, D. S.. Leukocyte telomere length in patients with schizophrenia: A meta-analysis. SCHIZOPHRENIA RESEARCH, v. 165, n. 2-3, p. 195-200, JUL 2015. (13/01352-8)

KERR, DANIEL SHIKANAI; STELLA, FLORINDO; RADANOVIC, MARCIA; APRAHAMIAN, IVAN; FERREIRA BERTOLLUCCI, PAULO HENRIQUE; FORLENZA, ORESTES VICENTE. Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder. BIPOLAR DISORDERS, v. 18, n. 1, p. 71-77, FEB 2016. (13/01352-8, 09/52825-8)