Anti-SYP monoclonal antibody, clone FQS2108-3

Oxidative stress is a key factor of and closely implicated in the pathogenesis of Alzheimer's disease (AD). We herein used tert-butyl hydroperoxide (t-BHP) to induce oxidative stress and mimic oxidative neurotoxicity in vitro. Lycopene is a natural antioxidant that has a strong ability to eliminate free radicals and shows effective protection in some neurodegenerative disease models. However, the effect of lycopene on t-BHP-induced neuronal damage in primary mouse neurons is unknown. This study aimed to investigate the effects of lycopene on t-BHP-induced neuronal damage and the related mechanisms. We found that lycopene pretreatment effectively enhanced the cell viability, improved the neuron morphology, increased the GSH/GSSG level, restored the mitochondrial membrane potential (m) and decreased reactive oxygen species generation. Furthermore, lycopene reduced the ratios of Bax:Bcl-2 and cleaved caspase-3:caspase-3 and the level of cytochrome C, increased the levels of synaptophysin (SYP) and postsynaptic density 95 (PSD95) and activated the PI3K/Akt pathway. In conclusion, lycopene attenuated oxidative stress and reduced t-BHP-induced cell apoptosis, and the mechanism is likely related to activation of the PI3K/Akt pathway. Therefore, lycopene is a potential agent for preventing oxidative stress-mediated AD.

Background Intense exercise can cause injury and apoptosis, but few studies have reported its effect on the central nervous system (CNS). The initial reason for hippocampus injury is the excitotoxicity of glutamate and calcium overload. Intracellular free Ca2+ ([Ca2+]i) overload may trigger the apoptosis pathway and neuron damage. The aim of this study was to investigate whether intense exercise could cause hippocampus apoptosis and neuron damage and then to determine which pathway was activated by this apoptosis. Methods We used one bout of swimming exhaustion rats as models. Intracellular ([Ca2+]i) was measured to estimate the calcium overload by Fura-2/AM immediately after exhaustion; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were performed for estimating astrocyte activation and synapse plasticity 24 hours after exhaustion. Apoptosis cells were displayed using dUTP nick end labelling (TUNEL) stain; endoplasmic reticulum (ER) stress-induced apoptosis pathway and mitochondrial apoptosis pathway were synchronously detected by Western blotting. Results An increasing level of intracellular [Ca2+]i (P<0.01) was found in the hippocampus immediately after exhaustion. GFAP and SYP immunofluorescence showed that the astrocytes are activated, and the synapse plasticity collapsed significantly 24 hours after exhaustion. TUNEL stain showed that the number of apoptosis cells were notably raised (P<0.01); Western blotting of the apoptosis pathway showed increasing levels of caspase-3 cleavage (P<0.01), Bax (P<0.01), caspase-12 cleavage (P<0.01), C/EBP-homologous protein (CHOP) (P<0.01), and phospho-Junamino-terminal kinases (p-JNK; P<0.01) and decreasing level of Bcl-2 (P<0.01). Our results proved that exhaustion can induce hippocampus injury and apoptosis by [Ca2+]i overload, with collapsed synaptic plasticity as the injury pattern and ER stress-induced apoptosis as the activated pathway. Conclusion Intense exercise can cause excessive apoptosis and synapse plasticity damage in the hippocampus with [Ca2+]i overload as the initial reason, and thus provides leads for therapeutic interventions in the brain health of athletes.