Crocin Treatment after Maternal Hypoxia Attenuates Spatial Memory Impairment and Expression of BACE1 and HIF-1α in Rat Offspring Brain

Abstract

Objective: Hypoxia via expression of Hypoxia Inducible Factor-1 (HIF-1) is an important and effective factor in the onset and progression of memory disorders such as Alzheimer Disease (AD). The activity of β-secretase (BACE1) increased in hypoxia condition. BACE1 trigger a cascade of pathological events resulting in AD. Crocin act as memory improvement agent but its molecular mechanism is not well-known. So, in this study, the effect of crocin on spatial memory, HIF-1α and BACE1 gene expression were investigated in rat offspring under maternal hypoxia. Materials and methods: Female pregnant rats on the 20th day of pregnancy were divided into 4 groups including: sham, crocin treated, hypoxia and hypoxia group treated with crocin. In hypoxia groups, pregnant rats were exposed to the 7% oxygen and 93% nitrogen intensity for 3 hours. In the crocin treated group, crocin (30 mg/kg) injected at P14-28, (i.p). At the end, Morris water maze was used to assess spatial memory and Real-Time PCR analysis was performed to measure the expression of BACE1 and HIF-1α genes in the brain of offspring. Results: Maternal hypoxia impaired memory task compared to the sham group. But crocin treatment improved cognitive behavior. HIF-1α and BACE1 expression were unregulated in the brain of offspring in hypoxia group. Crocin treatment could attenuate the expression of both genes. Conclusion: According to our results, down- regulation of HIF-1α and BACE1 gene expression in the brain of rat offspring after crocin treatment can be suggested as molecular mechanism for crocin to improve spatial memory.

Keywords

• maternal hypoxia
• spatial memory
• rat offspring
• crocin
• hif1
• bace1