Neuroprotective effects of sildenafil against oxidative stress and memory dysfunction in mice exposed to noise stress.
Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level. Sildenafil (15mg/kg) was orally administered 30min before noise exposure for 14days. Behavioral assessments were performed using novel object recognition (NOR) test and radial arm maze (RAM) test. Higher levels of memory dysfunction and oxidative stress were observed in noise alone-induced mice compared to control group. Interestingly, sildenafil administration increased memory performance, decreased oxidative stress, and increased neuroprotection in the hippocampus region of noise alone-induced mice likely through affecting memory related pathways such as cGMP/PKG/CREB and p25/CDK5, and induction of free radical scavengers such as SOD1, SOD2, SOD3, Prdx5, and catalase in the brain of stressed mice.
Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Hu Erxidan
HE
Sikandaner
Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
So Young
SY
Park
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Min Jung
MJ
Kim
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: snparkmd@catholic.ac.kr.
Shi Nae
SN
Park
Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: neuroman@catholic.ac.kr.
Dong Won
DW
Yang
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D007211:Indoles / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009622:Noise / Q000009:adverse effects; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000150:complications* / Q000209:etiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D007211:Indoles; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016875:tau Proteins; C024139:indole-3-lactic acid; D000068677:Sildenafil Citrate; D013482:Superoxide Dismutase; D050882:CREB-Binding Protein; D009638:Norepinephrine
Behavior; Cognition; Memory; Noise; Oxidative stress; Phosphodiesterase type 5 inhibitors; Sildenafil