IC‐P3‐228: The protective effect of analog 165 of APP5‐mer peptide on synapses of neuron in hippocampus of STZ‐AD rats

Alzherimer's disease (AD) is a chronic neurodegenerative disorder .Deficiency of synapses and destruction of synaptic construction has been found in AD. Streptozotocin (STZ) injection in the brain is known to cause cognitive impairment and prolonged impairment in glucose and energy metabolism. The model is likened to sporadic AD in humans. It is not known whether STZ is associated with synaptic signal transduction. Analog 165 of APP 5-mer peptide is effective in protecting neurons. Based on affecting expression and activity of survival/death related proteins in neurons, it can implement neuroprotection. A total of 45 Wistar rats were randomly divided into control group, model group and treated group. The rats in the model and treated group received intracerebroventricular injection of STZ bilaterally. After three weeks, the rats in treated group received gastric perfusion of analog 165 of APP5-mer peptide. After the four-week treatment, the memory of the rats was surveyed by Morris water maze test, the expression of synaptic associated proteins, such as PSD-95, synaptophysin and α-Synuclein were tested with immunohistochemical staining and Western blotting, the ultra-structure of neuron of hippocampus was observed with transmission electron microscope. Full-course swimming time was obviously longer in model group than these in treated and control group. In model group, the expression of PSD-95 and synaptophysin decreased, expression of α-Synuclein increased. Treated group normalized the expression of the targeted proteins. Retrograde degeneration of neuron of hippocampus was observed In model group, and dysmorphic synapses were observed In the neuropil. There were low PSD-95, synaptophysin levels and high α-Synuclein levels in the brain of ICV injection of STZ rats. Analog 165 of APP5-mer peptide improves the expression of the three proteins to some extent; therefore it may protect synapse and improve learning ability and memory.