Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice

NEUROBIOLOGY OF AGING

卷:35

Article

Puzzo, Daniela¹  Loreto, Carla²  Giunta, Salvatore²  Musumeci, Giuseppe²  Frasca, Giuseppina¹  Podda, Maria Vittoria³  Arancio, Ottavio⁴  Palmeri, Agostino¹ 

[1] Univ Catania, Physiol Sect, Dept Biomed Sci, Catania, Italy

[2] Univ Catania, Sect Anat, Dept Biomed Sci, Catania, Italy

[3] Univ Cattolica Sacro Cuore, Sch Med, Inst Human Physiol, I-00168 Rome, Italy

[4] Columbia Univ, Dept Pathol & Cell Biol, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA

关键词: Aging;    Sildenafil;    Apoptosis;    Caspase-3;    Bax/Bcl-2 ratio;    BDNF;    APP processing;    Beta-amyloid;   

DOI  :  10.1016/j.neurobiolaging.2013.09.002

来源: Elsevier

【 摘 要 】

Age-related cognitive decline is accompanied by an increase of neuronal apoptosis and a dysregulation of neuroplasticity-related molecules such as brain-derived neurotrophic factor and neurotoxic factors including beta amyloid (A beta) peptide. Because it has been previously demonstrated that phosphodiesterase-5 inhibitors (PDE5-Is) protect against hippocampal synaptic dysfunction and memory deficits in mouse models of Alzheimer's disease and physiological aging, we investigated the effect of a treatment with the PDE5-I, sildenafil, on cell death, pro-and antiapoptotic molecules, and Ab production. We demonstrated that chronic intraperitoneal injection of sildenafil (3 mg/kg for 3 weeks) decreased terminal deoxyuridine triphosphate nick end labeling-positive cells in the CA1 hippocampal area of 26-30-month-old mice, downregulating the proapoptotic proteins, caspase-3 and B-cell lymphoma 2-associated X, and increasing antiapoptotic molecules such as B-cell lymphoma protein-2 and brain-derived neurotrophic factor. Also, sildenafil reverted the shifting of amyloid precursor protein processing toward A beta 42 production and the increase of the A beta 42:A beta 40 ratio in aged mice. Our data suggest that PDE5-I might be beneficial to treat age-related detrimental features in a physiological mouse model of aging. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

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