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

Maria Vittoria Podda, Daniela Puzzo, Carla Loreto, Salvatore Giunta, Giuseppe Musumeci, Giuseppina Frasca, Ottavio Arancio, Agostino Palmeri

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57 Citazioni (Scopus)

Abstract

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 (Aβ) 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 Aβ 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 Aβ42 production and the increase of the Aβ42:Aβ40 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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine12
RivistaNeurobiology of Aging
Volume2013
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • BDNF
  • Bax/Bcl2 ratio
  • aging
  • apoptosis
  • beta-amyloid
  • sildenafil

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