Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Protective effects of vitamin B12 against LPS-induced cognitive impairment through modulation of neuroinflammation, oxidative stress, and cholinergic dysfunction

Articles in Press

Document Type : Original Article

Authors
Zahra Khosravi 1, 2
Rasul Saberi 1, 3
Sajjad Mollaei 3
Elham Taheri 2
Afsaneh Hokmabadi 4
Zahra Kioumarsi Darbandi 1, 3
Hasan Hazimeh 5
Arezoo Rajabian 6, 7
Mahmoud Hosseini 1, 3
1 Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Clinical Psychology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4 Department of Anatomy and Cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
7 Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ijbms.2026.94516.20428
Abstract
Objective(s): Neuroinflammation is a key pathological driver of cognitive impairment in neurodegenerative diseases. The endotoxin lipopolysaccharide (LPS) is used to model neuroinflammation, memory impairment, and neurodegeneration. Vitamin B12 has been extensively studied as an anti-oxidant and anti-inflammatory compound that plays an important role in neurological health. The protective effects of vitamin B12 against LPS-induced cognitive impairment, neuroinflammation, oxidative stress, and cholinergic dysfunction were investigated.
Materials and Methods: Male Wistar rats were randomly assigned to five groups (n=10 per group): Control, LPS (1 mg/kg, intraperitoneal injection), and three LPS+vitamin B12 (cyanocobalamin) groups receiving 0.25, 0.5, or 1 mg/kg of vitamin B12 by oral gavage. The Morris water maze and passive avoidance tests were conducted, and tissue samples were used to assess oxidative stress, inflammatory markers, and cholinergic activity in the animals’ brains.
Results: Vitamin B12 significantly improved memory in the Morris water maze and passive avoidance tests compared with the LPS group (P<0.001), with higher doses being more effective. Vitamin B12 also attenuated oxidative stress and the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 (P<0.05-0.001). It also significantly decreased acetylcholinesterase activity (P<0.01-0.001), while the highest dose significantly increased the expression of muscarinic acetylcholine receptor 1 (P<0.01).
Conclusion: These findings suggest that B12 may reduce inflammation and oxidative stress, modulate the cholinergic system, and have potential for the prevention and treatment of neuroinflammation and inflammation-induced memory impairment.
Keywords
Cholinergic System
Learning
Lipopolysaccharides
Memory
Oxidative stress
Vitamin B12
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 12 September 2026