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.

Puzzo, D., Loreto, C., Giunta, S., Musumeci, G., Frasca, G., Podda, M. V., Arancio, O., Palmeri, A., Effect of phosphodiesterase-5 inhibition on apoptosis and Aβ load in aged mice, <<NEUROBIOLOGY OF AGING>>, N/A; 2013 (N/A): N/A-N/A. [doi:10.1016/j.neurobiolaging.2013.09.002.] [http://hdl.handle.net/10807/52369]

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

Podda, Maria Vittoria;
2013

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.
Inglese
Puzzo, D., Loreto, C., Giunta, S., Musumeci, G., Frasca, G., Podda, M. V., Arancio, O., Palmeri, A., Effect of phosphodiesterase-5 inhibition on apoptosis and Aβ load in aged mice, <<NEUROBIOLOGY OF AGING>>, N/A; 2013 (N/A): N/A-N/A. [doi:10.1016/j.neurobiolaging.2013.09.002.] [http://hdl.handle.net/10807/52369]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/52369
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