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

OBJECTIVES

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.