Salmon milt extract is known to improve impaired brain function in animal models with brain disease and contains high levels of nucleic acids. The purpose of the present study is to clarify the effect of hydrolyzed salmon milt extract (HSME) and its nucleic acid fraction (NAF) on brain function in normal mice. A diet containing 2.5% HSME or NAF, but not normal diet, induced normal mice to devote more time in exploring novel and moved objects than in exploring familiar and unmoved objects, as observed during novel object recognition and spatial recognition tests, respectively, suggesting that nucleic acids in HSME may enhance brain function. Quantitative PCR analysis revealed that expression of marker genes for neural stem cells (NSCs) and glial cells, followed by those of neurons, was up-regulated after start of the ingestion. Exposure of primary cultured NSCs to HSME, NAF, and oligonucleotides significantly increased MTT reduction activity and cellular ATP level, suggesting that nucleic acids directly promote proliferation in NSCs. Thus, oral ingestion of nucleic acids enhances brain function in normal mice, and this effect may be at least partially provoked by increase in proliferation of NSCs.