Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Abstract

Living in an enriched environment (EC) during development enhances memory function in adulthood; living in an impoverished environment (IC) impairs memory function. Compounds previously demonstrated to improve memory among IC rats include CDP-choline and uridine monophosphate (UMP). Brain phosphatidylcholine (PC) synthesis utilizes both the uridine formed from the metabolism of exogenous CDP-choline and UMP, and the choline formed from that of CDP-choline. It also uses the polyunsaturated fatty acid (PUFA) DHA, a precursor for the diacylglycerol incorporated into PC. DHA administration also improves cognition in young and aged rodents and humans; its effects on cognitively impaired IC rats have not been characterized. We have thus examined the consequences of administering DHA (300 mg/kg) by gavage, UMP (0.5% in the diet), or both compounds on hippocampal- and striatal-dependent forms of memory among rats exposed to EC or IC conditions for 1 month starting at weaning, and consuming a choline-containing diet. We observe that giving IC rats either dietary UMP or gavaged DHA improves performance on the hidden version of the Morris water maze (all P<0.05), a hippocampal-dependent task; co-administration of both phosphatide precursors further enhances the IC rats' performance on this task (P<0.001). Neither UMP nor DHA, nor giving both compounds, affects the performance of EC rats on the hidden version of the Morris water maze (P>0.05), nor the performance by IC or EC rats on the visible version of the Morris water maze (all P>0.05), a striatal-dependent task. We confirm that co-administration of UMP and DHA to rats increases brain levels of the phosphatides PC, PE, SM, PS, PI, and total brain phospholipid levels (all P<0.05), and show that rearing animals in an enriched environment also elevates brain PC, PS, and PI levels (all P<0.01) and total brain phospholipids (P<0.01) compared with their levels in animals reared in an IC environment. These findings suggest that giving DHA plus UMP can ameliorate memory deficits associated with rearing under impoverished conditions, and that this effect may be mediated in part through enhanced synthesis of brain membrane phosphatides.

Figure 1. Morris water maze - Hidden

The effects of environment, UMP, and DHA administration on memory for a hippocampal-dependent hidden platform water maze in rats reared under EC or IC conditions for 1 month immediately postweaning. Values are means ± SEM, n=12. A. IC rats administered UMP, DHA, or UMP and DHA had decreased escape latencies compared to the IC control rats (all P< 0.05). B. EC rats administered UMP, DHA, or UMP and DHA did not have decreased escape latencies compared to the EC control rats (all P>0.05) C. The 60 sec probe test was effected by environment (P<0.042), quadrant (P<0.001), and diet × environment interaction (P<0.05).

Figure 2. Morris water maze - Visible

The effects of environment, UMP, and DHA administration on memory for a striatal-dependent visible platform water maze in rats reared under EC or IC conditions for 1 month immediately postweaning. Values are means ± SEM, n=12. A. IC rats administered UMP, DHA, or UMP and DHA did not have decreased escape latencies compared to the IC control rats (all P> 0.05). B. EC rats administered UMP, DHA, or UMP and DHA did not have decreased escape latencies compared to the EC control rats (all P>0.05).

Figure 3. Rotarod

The effects of a UMP-supplemented diet and/or daily administration of DHA on IC and EC rats tested on an accelerating rotarod motor activity test. Values are mean ± S.E.M, n=12. The time spent on the rotarod was not affected (P’s.> .05)