BACKGROUND: Studies have shown that scorpion venom heat-resistant protein (SVHRP) exhibitsprotective effects on primary cultured hippocampal neurons.OBJECTIVE: To determine the effects of SVHRP on astrocyte activity and synaptic density in thehippocampus induced by amyloid β peptide 1-40 (Aβ_(1-40)) neurotoxicity.DESIGN, TIME AND SETTING: The randomized, controlled, animal experiment was performed atthe Central Laboratory, the Laboratory of Human Anatomy, and the Laboratory of Physiology, inDalian Medical University between March 2006 and June 2008.MATERIALS: Aβ_(1-40) was provided by Biosource, USA; SVHRP was a patented biological product ofDalian 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, Aβ, and SVHRP, with 9 rats in each group. Alzheimer’s disease was simulated with 10 μgAβ_(1-40) bilaterally injected into the hippocampus of the Aβ and SVHRP groups. The control group wasinjected with 2 μL 0.05% trifluoroacetic acid. One day following model establishment, the SVHRPgroup received an intraperitoneal injection of 2 μg/100 g SVHRP, while the control group and Aβgroup 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 areawas also detected. At 11 days following model establishment, escape latency, swimming time, anddistance to target quadrant were measured using the Morris water maze.RESULTS: Compared with the control group, the Aβ group exhibited notably reduced p38expression (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 timeand 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 decreasedGFAP expression in the rat hippocampus (P < 0.05). Water maze results demonstrated that escapelatency was significantly reduced (P < 0.05), and swimming time and distance to the target quadrantwere significantly prolonged.CONCLUSION: SVHRP inhibited exogenous Aβ_(1-40)-induced astrocyte activation and synapticdensity decline in the rat hippocampus. Place navigation and spatial searching results showed thatSVHRP blocked Aβ_(1-40)-induced impaired learning and memory. BACKGROUND: Studies have shown that scorpion venom heat-resistant protein (SVHRP) exhibitsprotective 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, inDalian 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, Aβ, and SVHRP, with 9 rats in each group. Alzheimer’s disease was simulated with 10 μgAβ_(1-40) bilaterally injected into the hippocampus of the Aβ and SVHRP groups. The control group wasinjecte d with 2 μL 0.05% trifluoroacetic acid. One day following model establishment, the SVHRPgroup received an intraperitoneal injection of 2 μg/100 g SVHRP, while the control group and Aβgroup 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 areawas also detected. At 11 days following model establishment, escape latency, swimming time, and distance to target quadrant was measured using the Morris water maze.RESULTS: Compared with the control group, the Aβ group exhibited notably reduced p38expression (P < 0.05 ) and notably increased GFAP expression in the rat hippocampus (P < 0.05). Water maze results reveal that escape latency was prolonged (P < 0.05), and swimming timeand distan Ce 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 decreasedGFAP expression in the rat hippocampus (P < 0.05). Water maze results revealed that escapelatency was significantly Reduced (P < 0.05), and swimming time and distance to the target quadrant significant significantly. CONCLUSION: SVHRP inhibited exogenous Aβ_(1-40)-induced astrocyte activation and synapticdensity decline in the rat hippocampus. Place navigation and spatial search results showed that SVHRP Blocked Aβ_(1-40)-induced impaired learning and memory.