N-acetylmannosamine improves object recognition and hippocampal cell proliferation in middle-aged mice

Sialic acids may modulate cell proliferation and gene expression, particularly in neural cells in vitro. However, the function of sialic acids in the central nervous system has not previously been examined. We examined whether N-acetylmannosamine (ManNAc) could improve object recognition and hippocampal cell proliferations in middle-aged mice. C56BL/6J mice aged 52 weeks were treated with ManNAc for 4 weeks. Their cognitive-ability was assessed with a place and object recognition test. ManNAc, but not N-acetylglucosamine or N-acetylneuraminic acid, improved the index score in the place recognition task at a dosage of 5.0 mg/mL in drinking water. Additionally, ManNAc enhanced the hippocampal cell proliferation, which was evaluated by a bromodeoxyuridine assay and the number of Ki67-immunoreactive cells. We could demonstrate that ManNAc had positive effects on the age-related brain dysfunction. These findings suggest that the use of ManNAc or related compounds may be a new approach for the treatment of human dementia.