Narjes Taherian - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
Gholamhassan Vaezi - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
Ali Neamati - Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
Leila Etemad - Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Vida Hsojjati - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
Mahmoud Gorji-Valokola - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): 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. Materials and Methods: 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.Results: 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.Conclusion: 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.

Estradiol benzoate, Hippocampus, Memory, Multiple Sclerosis, Vitamin B12