Tanshinone ⅡA improves memory deficits by inhibiting the endoplasmic reticulum stress and apoptosis in Alzheimer's disease mice / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the protective effects of tanshinone ⅡA (tan ⅡA) against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease. Methods: Kunming mice were randomly divided into five groups (n=10 in each group) control group, STZ group, and tan ⅡA low, medium and high groups. Mice in the STZ and three tan ⅡA groups were given intracerebroventrically injection of STZ (3 mg/kg bilaterally, on day 1 and day 3). Tan ⅡA (20, 40, and 80 mg/kg every day) was administered intragastrically for 28 days starting from the first dose of STZ. Learning and memory were evaluated with a Morris water maze (MWM) test. Nissl method was used to observe neurons damage in the cortex and the hippocampus, and Western blot method to analyze endoplasmic reticulum stress markers and apoptosis signaling proteins. Results: Daily treatment with tan ⅡA showed a dose-dependent improvement in STZ-induced memory deficits. Nissl staining results confirmed the protective effects of tan ⅡA on cortical and hippocampal neurons damage induced by STZ. In addition, tan ⅡA markedly prevented STZ-induced abnormal expression of glucose regulated protein 78 (GRP78), initiation factor 2α (eIF2α), activating transcription factor 6 (ATF6), as well as suppressed the activation of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) pathways. Moreover, tan ⅡA induced an up-regulation of the Bcl-2/Bax ratio and down-regulation of cleaved caspase-3 protein activity. Conclusion: Tan ⅡA prevents STZ-induced memory deficits, which may be attributed to attenuating endoplasmic reticulum stress and neuronal apoptosis.