Objective: This study aimed to investigate the effects of combined environmental enrichment (EE) and (-)-Epigallocatechin-3-gallate (EGCG) on cognitive function and hippocampal factors in a rat model of streptozotocin (STZ)-induced Alzheimer-like disease.
Materials and methods: Adult rats were divided to five groups: Sham, Alzheimer (ALZ), ALZ+EGCG, ALZ+EE, and ALZ+EE+EGCG. Alzheimer's disease (AD) was induced by intracerebroventricular (ICV) injection of STZ (3 mg/kg). EGCG was administered orally (10 mg/kg) once daily for 21 consecutive days, and EE rats were housed in a large enriched cage (50×50×50 cm) containing various objects for 28 days. Spatial memory was assessed using the Morris water maze (MWM), and hippocampal gene expression of Amyloid Precursor Protein (APP) and Brain Derived neurotrophic Factor (BDNF) was measured by real-time PCR.
Results: STZ reduced learning performance during the training phase of the MWM by about 60% compared with the Sham group. Although all treated groups showed slight improvement compared with the STZ group, none significantly enhanced learning rate. In the probe test, STZ caused a severe memory deficit compared with baseline (p<0.001), while the combined treatment of EE and EGCG significantly improved memory and restored performance to the normal levels (p>0.05). STZ increased hippocampal APP expression compared with Sham (p<0.01), while combination treatment significantly reduced APP expression (p<0.001). Conversely, BDNF expression decreased in AD rats compared with Sham and was significantly upregulated by EE+EGCG combination (p<0.01).
Conclusion: These findings indicate that combined EE and EGCG treatment ameliorates memory deficits in AD rats, potentially through modulation of hippocampal APP and BDNF. Such interventions along with medical treatments may help to mitigate cognitive impairments in this clinical population.