Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils

Abstract

This study examined the effects on cognitive behaviors of giving normal adult gerbils three compounds, normally in the circulation, which interact to increase brain phosphatides, synaptic proteins, dendritic spines, and neurotransmitter release. Animals received supplemental uridine (as its monophosphate, UMP; 0.5%) and choline (0.1%) via the diet, and docosahexaenoic acid (DHA; 300 mg/kg/day) by gavage, for 4 wk, and then throughout the subsequent period of behavioral training and testing. As shown previously, giving all three compounds caused highly significant (P<0.001) increases in total brain phospholipids and in each major phosphatide; giving DHA or UMP (plus choline) produced smaller increases in some of the phosphatides. DHA plus choline improved performance on the four-arm radial maze, T-maze, and Y-maze tests; coadministering UMP further enhanced these increases. (Uridine probably acts by generating both CTP, which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis. All three compounds also act by enhancing the substrate-saturation of phosphatide-synthesizing enzymes.) These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals.

Figures

Figure 1.

The effects of a UMP-supplemented diet and/or daily administration of DHA on acquisition of a four-arm radial maze with two arms baited in gerbils. Values are means ± se; n = 12. A) Reference memory errors (UMP, P<0.038; DHA, P<0.042; UMP×DHA, P<0.001). B) Working memory errors (UMP, P<0.029; DHA, P<0.035; UMP×DHA, P<0.001). C) Total errors (UMP, P<0.022; DHA, P<0.034; UMP×DHA, P<0.001).

Figure 2.

The effects of a UMP-supplemented diet and/or daily administration of DHA on acquisition of a T maze with one arm baited in gerbils. Values are means ± se; n = 12. A) Acquisition of the task was affected (sessions to reach criterion: UMP, P<0.038; DHA, P<0.024; UMP×DHA, P<0.017). B) Retention of the task was affected (percentage correct in a 24-h delay memory test: UMP, P<0.04; DHA, P<0.036; UMP×DHA, P<0.021).

Figure 3.

The effects of a UMP-supplemented diet and/or daily administration of DHA on acquisition of a Y maze with a 4-day delay memory test. Values are means ± se; n = 12. Retention of the task was affected (percentage correct: UMP, P<0.012; DHA, P<0.009; UMP×DHA, P<0.001).

Figure 4.

The effects of a UMP-supplemented diet and/or daily administration of DHA on an accelerating rotarod motor activity test. Values are means ± se; n = 12. The time spent on the rotarod was not affected by any treatment (P>0.05).