Trideoxycytidine Diphosphate Promotes Neural Stem Cell Proliferation and Neurogenesis in Mice

Area of Science:

• Nutritional Neuroscience
• Molecular Biology
• Neurogenesis Research

Background:

• Food-derived nucleic acids possess biological activities and nutritional value.
• Salmon milt extract hydrolysates' nucleic acid fraction (NAF) improves cognitive function in mice, but active components and mechanisms remain unidentified.

Purpose of the Study:

• To identify specific active ingredients within NAF that enhance cognitive function.
• To elucidate the underlying molecular mechanisms responsible for cognitive enhancement.

Main Methods:

• Screened 64 trideoxyribonucleotides for proliferative effects on primary cultured neural stem cells (pcNSCs).
• Administered the identified active trideoxyribonucleotide (trideoxycytidine diphosphate - CCC) intrahippocampally and orally in mice.
• Evaluated neurogenesis and spatial memory, alongside proteomic and western blot analyses to determine the mechanism of action.

Main Results:

• Trideoxycytidine diphosphate (CCC) significantly promoted pcNSC proliferation.
• CCC administration in mice increased hippocampal neurogenesis and enhanced spatial memory.
• Proteomic analysis identified alterations in PI3K-Akt signaling proteins, with CCC increasing Akt phosphorylation, mediated by eEF1A2.

Conclusions:

• Trideoxycytidine diphosphate (CCC), a simple food-derived molecule, stimulates neural stem cell proliferation.
• CCC enhances neurogenesis through the eEF1A2/PI3K-Akt signaling pathway.
• This pathway activation contributes to improved cognitive function.