Vitamin B12 and estradiol benzoate improve memory retrieval through activation of the hippocampal AKT, BDNF, and CREB proteins in a rat model of multiple sclerosis

Multiple sclerosis (MS) causes extensive damage in the hippocampus. Vitamin B12 (vit B12) and estradiol benzoate (EB) have the anti-inflammatory and re-myelination properties that make them proper in improvement of cognitive impairment. The goal of this study is to evaluate the effect of these compounds on learning and memory disturbances.

77 adult male rats were implanted with stainless steel guide cannula bilaterally into the hippocampal area. The animals received 3 μl intrahippocampal EtB 0.01% and were accidentally divided into eleven groups (7 rats/group). The groups were included control, peanut oil (sham1), distilled water (sham 2), vit B12 (0.25, 0.5, 1 mg/kg), EB (25 and 50 mg/kg), vit B12 (0.25 mg/kg) plus EB (25 mg/kg), vit B12 (0.5 mg/kg) plus EB (25 mg/kg), and vit B12 (1 mg/kg) plus EB (50 mg/kg). Control group received intrahippocampal saline (as solvent). The locomotor activity and learning and memory functions were evaluated by the open-field and shuttle-box tests, respectively. AKT, CREB and BDNF levels were analyzed by western blotting.

This study has found significant deficit in passive avoidance learning, locomotor activity, as well as decrease at the level of phosphorylated AKT, BDNF, and CREB in groups that received EtB. Vit B12 (1 mg/kg), EB (50 mg/kg) and their combination markedly improved these side effects.

This study demonstrated that vitamin B12 and estradiol benzoate, especially in combination therapy, can be helpful in treatment of memory problems, MS- induced dysfunction through activation of the hippocampal AKT, BDNF, and CREB proteins.