Crocin mitigated cognitive impairment and brain molecular alterations induced by different intensities of prenatal hypoxia in neonatal rats.

INTRODUCTION: Brain hypoxia has important role to the onset and progression of sporadic form of Alzheimer disease via expression of hypoxia-inducible factor-1 (HIF-1). Crocin by anti-amyloidogenic property inhibits ß-amyloid formation. However, the molecular mechanism associated with anti-amyloidogenic activity of crocin is unknown. So, the present study was designed to investigate the effect of crocin on cognitive behavior and expression of HIF-1α and ß-secretase (BACE1) genes in the brain of neonate rats following different intensities of hypoxia during pregnancy. MATERIAL AND METHODS: Pregnant female rats were divided into six groups including sham, control crocin treated (CC), hypoxia with three different intensities (H1-H3), and most intense of hypoxic group treated with crocin (H3C) (30 mg/kg; i.p) at P14. Hypoxia induced on the 20th day of pregnancy. Animals in sham and CC were put in hypoxia chamber at the same time of hypoxia group without any hypoxia induction. Morris water maze (MWM) and qRT-PCR were used to evaluate the cognitive behavior and mRNA levels of BACE1 and HIF-1α genes in the brain tissues. RESULTS: Animal under 7% O2  + 93% N2 condition for 3 hr showed the highest cognitive behavior impairment and upregulated HIF-1α and BACE1 mRNA in brains of offspring (p < .001). Crocin treatment improved memory impairment and attenuated the gene expression of HIF-1α and BACE1 in the brains of neonate rat. CONCLUSIONS: It was concluded that crocin has beneficial effects on the brain of neonate rats under gestational hypoxia by improvement of memory impairment and molecular alteration related to hypoxia.

Study the effect of crocin in three maternal hypoxia protocols with different oxygen intensities on motor activity and balance in rat offspring.

Hypoxia as one of the most common clinical disturbances in pregnancy period can cause destructive changes in motor sensory cortex and can lead to imperfect organization in motor reactions. Crocin, a water-soluble carotenoid, is the most active ingredients of saffron and a lot of studies declare its positive effectiveness on improving motor activity. Since the hypoxia intensity affects its malicious amount on movement, in this paper, we have studied the effect of crocin in three maternal hypoxia protocols with different oxygen intensities on motor activity and balance in rat offspring. In this experiment, female rats (Wistar) were used on the 20th day of pregnancy. The rats were randomly divided into eight experimental groups: sham, crocin, hypoxia with three different intensities: 10% oxygen and 90% nitrogen for 1 h (hypoxia-ɪ), 7% oxygen and 93% nitrogen for 1 h (hypoxia-ɪɪ), 7% oxygen and 93% nitrogen for 3 h (hypoxia-ɪɪɪ) and treated-crocin hypoxia groups. To produce hypoxia, pregnant rats were placed in a hypoxia box. In crocin group, rat offspring received 30 mg/kg crocin via IP injection at P14-28. Control group also received saline injection at the same time. Finally, balance and motor activity in offspring were measured respectively by rotarod and open-field devices. Results showed that motor activity significantly decreased in hypoxia-ɪɪɪ group as compared with sham group (p < 0.01). Balance in hypoxia-ɪɪɪ group significantly decreased as compared with sham group (p < 0.05). As a result, crocin treatment improved all these changes. The results of this study implied that both hypoxia duration and intensity have profound effects on motor activities impairments.