Neuronal Cell Cycle Re-Entry Markers are Altered in the Senescence Accelerated Mouse P8 (SAMP8)

Article type: Research Article

Authors: Casadesús, Gemma^c | Gutierrez-Cuesta, Javier^{a; e} | Lee, Hyoung-gon^d | Jiménez, Andrés^a | Tajes, Marta^{a; e} | Ortuño-Sahagún, Daniel^b | Camins, Antoni^a | Smith, Mark A.^d | Pallàs, Mercè^{a; *}

Affiliations: [a] Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain | [b] Laboratorio de Desarrollo y Regeneración Neural, Instituto de Neurobiología, Departamento de Biología Celular y Molecular, C.U.C.B.A, Universidad de Guadalajara, Guadalajara, Jalisco, México | [c] Departments of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA | [d] Departments of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA | [e] Present address: Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain

Correspondence: [*] Correspondence to: Mercè Pallàs, PhD, Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Universitat de Barcelona. Avd. Diagonal, 643. E-08028 Barcelona, Spain. E-mail: [email protected].

Abstract: Senescence-accelerated mice 8 (SAMP8), a model of aging, display many established pathological features of Alzheimer's disease (AD); however, whether cell cycle alterations exist in these animals remains unknown. Given that these animals present changes such as tau phosphorylation and redox imbalance, both associated with cell cycle alterations, we determined whether changes in cell cycle markers were present in SAMP8 and SAMR1 (control strain) at 3, 6, and 9 months-old brains. As expected, an increase in tau hyperphosphorylation and its associated machinery, i.e., cdk5 and GSK3β, was observed both between strains and also with aging. Particularly, significant differences in cyclin A, cyclin D1, cyclin E, Cdk2, cyclin B, pR, and E2F1 were found when comparing SAMP8 to SAMR1. More interestingly, a partial correlation with several cell cycle markers described in AD brain is found in SAMP8, indicating that some specific hallmarks of AD are also present in this strain, which has been postulated as an early switch model of the disease.

Keywords: Aging, Alzheimer's disease, cdk5, cell cycle, GSK3β, tau

DOI: 10.3233/JAD-2012-120112

Journal: Journal of Alzheimer's Disease, vol. 30, no. 3, pp. 573-583, 2012