Lithium effect over microRNAs expression induced by amyloid-beta in primary culture of hippocampal neurons

• Grant number: 11/20295-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2012
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Daniel Shikanai Kerr
• Grantee: Victor Junji Yamamoto
• 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

Abstract

Alzheimer's disease (AD), supposed to affect 35 million people around the world, is the most common cause of dementia. Despite important pathophysiologic mechanisms have been discovered, there is no effective treatment yet. Recent publications suggest lithium as a possible treatment for AD, not only for its progression, but also prevention. These studies investigate the neuroprotective and neurotrophic properties of lithium, which regulates apoptotic and anti-apoptotic pathways. Several alterations in gene and protein expression have already been described in AD, including those caused by microRNA (miRNA) regulation. miRNAs are small non-coding RNA molecules constituted by approximately 22 nucleotides, whose pathway serves as an important post transcriptional regulation mechanism. We propose to study lithium effects on miRNAs expression in a primary culture of hippocampal neurons treated with amyloid-² peptide (AB). Neuronal culture treated with AB is a well-established model of neurodegeneration in vitro used to study AD. It has already been showed that AB can alter the expression of some miRNAs in primary neuronal culture, but the metabolic pathways altered by lithium are not completely known. We plan to extend AD pathophysiology knowledge, identifying differentially expressed miRNAs as a result of AB treatment as well as verifying lithium effect on this model. Lastly, this study may show possible effects of lithium, related to miRNAs modulation in AB toxicity. (AU)