BACKGROUND: Studies have shown that scorpion venom heat-resistant protein (SVHRP) exhibits protective effects on primary cultured hippocampal neurons.OBJECTIVE: To determine the effects of SVHRP on astrocyte activity and synaptic density in the hippocampus induced by amyloid β peptide 1-40 (Aβ_(1-40)) neurotoxicity.DESIGN, TIME AND SETTING: The randomized, controlled, animal experiment was performed at the Central Laboratory, the Laboratory of Human Anatomy, and the Laboratory of Physiology, in Dalian Medical University between March 2006 and June 2008.MATERIALS: Aβ_(1-40) was provided by Biosource, USA; SVHRP was a patented biological product of Dalian Medical University (No. ZL01 1 06166.9).METHODS: A total of 27 healthy, 2-month-old, male SD rats were randomly assigned to 3 groups:control, Ap, and SVHRP, with 9 rats in each group. Alzheimer's disease was simulated with 10 μg Aβ_(1-40) bilaterally injected into the hippocampus of the Ap and SVHRP groups. The control group was injected with 2 μL 0.05% trifluoroacetic acid. One day following model establishment, the SVHRP group received an intraperitoneal injection of 2 μg/100 g SVHRP, while the control group and Aβ group received 0.5 mL/100 g tri-distilled water, once per day, for 10 consecutive days.MAIN OUTCOME MEASURES: At 16 days following model establishment, synaptophysin (p38) expression in CA1-CA4 regions of the rat hippocampus was determined by immunohistochemistry.Glial fibrillary acidic protein (GFAP) expression surrounding the hippocampal Aβ_(1-40) injected area was also detected. At 11 days following model establishment, escape latency, swimming time, and distance to target quadrant were measured using the Morris water maze.RESULTS: Compared with the control group, the Ap group exhibited notably reduced p38 expression (P< 0.05) and notably increased GFAP expression in the rat hippocampus (P< 0.05).Water maze results demonstrated that escape latency was prolonged (P< 0.05), and swimming time and distance to the target quadrant were shortened in the Aβ group. Compared with the Aβ group,the SVHRP group exhibited notably increased p38 expression (P< 0.05) and notably decreased GFAP expression in the rat hippocampus (P < 0.05). Water maze results demonstrated that escape latency was significantly reduced (P < 0.05), and swimming time and distance to the target quadrant were significantly prolonged.CONCLUSION: SVHRP inhibited exogenous Aβ_(1-40)-induced astrocyte activation and synaptic density decline in the rat hippocampus. Place navigation and spatial searching results showed that SVHRP blocked Aβ_(1-40)-induced impaired learning and memory.