The effect of Arthrospira (Spirulina) maxima and its aqueous extract on fetal alcohol syndrome, induced in CD1 mice

The fetal alcohol syndrome is the most aggressive condition resulting from embryo-fetal ethanol exposure, characterized by a group of craniofacial and central nervous system dysmorphism, where the main altered brain structures are the cortex, the cerebellum, and the hippocampus. Ethanol exposure, particularly during the pregnancy, has shown to alter the neuronal activity in the hippocampus through the generation of reactive oxygen species (ROS). Arthrospira (Spirulina) maxima is a cyanobacterium that has been consumed in various parts of the world for several centuries. This cyanobacterium has various therapeutic and nutritional properties because of its high content of biologically active molecules such as tocopherols, β-carotenes, γ-linolenic acid, vitamins, minerals, and phycobiliproteins. Several reports indicate that A. maxima (Am) has a great protective capacity against toxic substances, viruses, and specially against damage produced by substances that generate ROS. This work aimed to evaluate the neuroprotective effect of Am and its aqueous extract (AmAE) rich in phycobiliproteins in two models of fetal alcohol syndrome in CD1 mice - prenatal and postnatal exposition to ethanol. In both models, pregnant mice were used, and they were distributed in six groups (n = 10) as follows: a) control (vehicle, purified water); b) vehicle plus EtOH 4 g/kg; c, d) Am (200 and 400 mg/kg, respectively) plus EtOH; and e, f) AmAE (100 and 200 mg/kg, respectively) plus EtOH. In the prenatal model, treatments were given to pregnant mice daily by gavage during the gestational days (GD) 0-15 (EtOH was given during GD6-15). While in postnatal model ethanol was administered directly to pups on the 7th postnatal day (PD). In both experiments, at PD45, mice were assessed in the light-dark box (LDB) and the Morris water maze (MWM) tests. Furthermore, their hippocampal neuronal density was determined by histological analysis in the dorsal hippocampus. The results showed greater alterations in the behavior and special memory of the animals of the prenatal study, while in postnatal exposure, similar trends that were not significant were found. The LDB test revealed a decrease in anxiety behavior at higher doses of Am and its AmAE, against the groups treated with purified water plus EtOH. However, in the MWM test, the performance of the high doses of Am and its AmAE improved significantly during the retention test. The histological analysis of dorsal hippocampus showed a decrease in the neuronal density of the different areas of the Ammon's horns (CA), by the EtOH exposure. However, in postnatal study, although there was a trend in neuronal decrease, it was not significant. Our conclusions indicate that prenatal exposure of EtOH produces greater alterations than postnatal exposure; the administration of Am and AmAE decreases the negative effects caused by prenatal and postnatal exposure to EtOH in spatial memory and anxiety behavior; doses of 400 mg/kg of Am and 200 mg/kg of AmAE have a greater protective effect against the neuronal loss in dorsal hippocampus; CA1 and CA3, the regions closely related with memory, are very affected in dorsal hippocampus during exposure to EtOH.