10–100μM sildenafil |
HT-22 hippocampal neuronal cells exposed to Aβ
25 - 35
|
Sildenafil rescued mitochondrial Ca2 + overload and dysfunction due to Aβ
25 - 35 by opening ATP-sensitive K + channels |
[140] |
20μM sildenafil |
HT-22 hippocampal neuronal cells exposed to advanced glycation end products |
Sildenafil decreased mitochondrial permeability transition pore opening and apoptosis via HO1 upregulation |
[141] |
Variable, 3 mg/kg |
Scopolamine-induced cholinergic dysfunction mice |
Sildenafil rescued memory |
[143] |
Variable, primarily 3 mg/kg/day intraperitoneal sildenafil |
APP/PS1 mice |
Sildenafil rescued long-term potentiation, CREB phosphorylation, memory, and decreased Aβ levels |
[144] |
6 mg/kg, intraperitoneal daily for 3 months |
APP/PS1 mice |
Sildenafil improved memory, amyloid plaque load, inflammation, and neurogenesis |
[145] |
2 mg/kg sildenafil twice daily for 4 months |
APP/PS1 mice |
Sildenafil rescued memory and amyloid pathology, downregulated PDE5, and increased NOS, NO, and cGMP levels |
[146] |
Sildenafil was dissolved in 0.9% saline at a concentration of 1.0 mg/ml. 10.0 mg/kg of this solution was administered intraperitoneally with an injection volume of 0.1 ml/10 g. |
APP/PS1 mice |
Sildenafil improved memory, decreased levels of Aβ, IL-1β, IL-6 and TNF-α, and increased p-CREB |
[147] |
15 mg/kg sildenafil daily for 10 weeks in water |
J20 mice |
Sildenafil improved memory, tau hyperphosphorylation, and Akt and GSK3β phosphorylation, but not prefrontal cortex Aβ
42 levels |
[61] |
15 mg/kg daily sildenafil, intraperitoneal |
Tg2576 AD mice |
Sildenafil improved memory, tau but not frontal cortex amyloid pathology, inhibited GSK3β, decreased CDK5 p25/35 ratio, upregulated BDNF and Arc |
[148] |
Variable |
Aged mice |
Sildenafil improved spatial memory retention but not acquisition |
[64] |
3 mg/kg intraperitoneal sildenafil daily for 3 weeks |
Aged mice |
Sildenafil decreased double-stranded DNA breaks and pro-apoptotic caspase-3 and Bax and upregulated antiapoptotic Bcl2 and BDNF |
[149] |
7.5 mg/kg sildenafil intraperitoneally once daily for 4 weeks |
SAMP8 mice |
Sildenafil improved amyloid and tau pathology, memory, and gliosis |
[145, 150] |
7.5 mg/kg sildenafil intraperitoneally once daily for 4 weeks |
SAMP8 mice |
Sildenafil decreased JNK phosphor-activation in the hippocampus, tau phosphorylation, and memory deficits |
[151] |
50 mg sildenafil, single dosage |
10 AD patients |
Sildenafil decreased spontaneous neural activity in right hippocampus |
[152] |
50 mg sildenafil, single dosage |
14 AD patients |
Sildenafil increased cerebral metabolic rate of oxygen and cerebral blood flow in 12 patients, decreased cerebral vascular reactivity in 8 patients |
[127] |