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

Autor(es)

Cardillo, Giancarlo de Mattos ^[1] ; Rodrigues De-Paula, Vanessa de Jesus ^{[1, 2]} ; Ikenaga, Eliza Hiromi ^[1] ; Costa, Luciana Rodrigues ^[1] ; Catanozi, Sergio ^[3] ; Schaeffer, Evelin Lisete ^[1] ; Gattaz, Wagner Farid ^[1] ; Kerr, Daniel Shikanai ^{[1, 4]} ; Forlenza, Orestes Vicente ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Lab Neurosci LIM 27, Inst Psiquiatria, Hosp Clin HCFMUSP, Rua Dr Ovidio Pires de Campos 785, BR-05403010 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Lab Psysbio LIM 23, Inst Psiquiatria, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, Lipids Lab LIM 10, Endocrinol & Metab Div, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil

^[4] Inst Fed Educ Ciencia & Tecnol Catarinense, Campus Camboriu, Camboriu, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ALZHEIMER'S DISEASE; v. 63, n. 1, p. 93-101, 2018.
• Citações Web of Science: 3

Resumo

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. (AU)

• Processo FAPESP: 14/14211-6 - Comprimento telomérico no sistema nervoso central de um modelo de Doença de Alzheimer tratado com lítio
• Beneficiário: Giancarlo de Mattos Cardillo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/52825-8 - Neurobiologia da doença de Alzheimer: marcadores de risco, prognóstico e resposta terapêutica
• Beneficiário: Wagner Farid Gattaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/01302-9 - Identificação das vias direta e indireta da inibição da glicogênio sintase kinase 3B pelo lítio em cultura de neurônios
• Beneficiário: Vanessa de Jesus Rodrigues de Paula
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado