Chronic Lithium Treatment Increases Telomere Length in Parietal Cortex and Hippocampus of Triple-Transgenic Alzheimer’s Disease Mice

Article type: Research Article

Authors: Cardillo, Giancarlo de Mattos^a | De-Paula, Vanessa de Jesus Rodrigues^{a; c} | Ikenaga, Eliza Hiromi^a | Costa, Luciana Rodrigues^a | Catanozi, Sergio^b | Schaeffer, Evelin Lisete^a | Gattaz, Wagner Farid^a | Kerr, Daniel Shikanai^{a; d} | Forlenza, Orestes Vicente^{a; *}

Affiliations: [a] Laboratory of Neuroscience (LIM-27), Instituto de Psiquiatria do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil | [b] Lipids Laboratory (LIM-10), Endocrinology and Metabolism Division of Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil | [c] Laboratory of Psysbio (LIM-23), Instituto de Psiquiatria do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, SP, Brazil | [d] Instituto Federal de Educacao, Ciencia e Tecnologia Catarinense-Campus Camboriu, Camboriu, SC, Brazil

Correspondence: [*] Correspondence to: Orestes V. Forlenza, Laboratory of Neuroscience (LIM-27), Instituto de Psiquiatria do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 Sao Paulo, SP, Brazil. E-mail: forlenza@usp.br.

Abstract: Telomere length (TL) is a biomarker of cell aging, and its shortening has been linked to several age-related diseases. In Alzheimer’s disease (AD), telomere shortening has been associated with neuroinflammation and oxidative stress. The majority of studies on TL in AD were based on leucocyte DNA, with little information about its status in the central nervous system. In addition to other neuroprotective effects, lithium has been implicated in the maintenance of TL. The present study aims to determine the effect of chronic lithium treatment on TL in different regions of the mouse brain, using a triple-transgenic mouse model (3xTg-AD). Eighteen transgenic and 22 wild-type (Wt) male mice were treated for eight months with chow containing 1.0 g (Li1) or 2.0 g (Li2) of lithium carbonate/kg, or standard chow (Li0). DNA was extracted from parietal cortex, hippocampus and olfactory epithelium and TL was quantified by real-time PCR. Chronic lithium treatment was associated with longer telomeres in the hippocampus (Li2, p = 0.0159) and in the parietal cortex (Li1, p = 0.0375) of 3xTg-AD compared to Wt. Our findings suggest that chronic lithium treatment does affect telomere maintenance, but the magnitude and nature of this effect depend on the working concentrations of lithium and characteristics of the tissue. This effect was observed when comparing 3xTg-AD with Wt mice, suggesting that the presence of AD pathology was required for the lithium modulation of TL.

Keywords: Alzheimer’s disease, hippocampus, lithium, olfactory epithelium, parietal cortex, telomere, transgenic mice

DOI: 10.3233/JAD-170838

Journal: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 93-101, 2018