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

Document Type : Original Article


1 Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

2 Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran

3 Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 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 anti-inflammatory and re-myelination properties that make them proper in improvement of cognitive impairment. This study aimed to evaluate the effects 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 randomly divided into eleven groups (7 rats/group). The groups 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). The control group received intrahippocampal saline (as solvent). The locomotor activity and learning and memory functions were evaluated by 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 in the levels 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 vit B12 and estradiol benzoate, especially in combination therapy, can be helpful in treatment of memory problems and MS-induced dysfunction through activation of the hippocampal AKT, BDNF, and CREB proteins.


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