Conjugated linoleic acid-enriched butter improved memory and up-regulated phospholipase A₂ encoding-genes in rat brain tissue

Reduced phospholipase A₂ (PLA₂) activity has been reported in blood cells and in postmortem brains of patients with Alzheimer disease (AD), and there is evidence that conjugated linoleic acid (CLA) modulates the activity of PLA₂ groups in non-brain tissues. As CLA isomers were shown to be actively incorporated and metabolized in the brains of rats, we hypothesized that feeding a diet naturally enriched in CLA would affect the activity and expression of Pla ₂ -encoding genes in rat brain tissue, with possible implications for memory. To test this hypothesis, Wistar rats were trained for the inhibitory avoidance task and fed a commercial diet (control) or experimental diets containing either low CLA- or CLA-enriched butter for 4 weeks. After this period, the rats were tested for memory retrieval and killed for tissue collection. Hippocampal expression of 19 Pla ₂ genes was evaluated by qPCR, and activities of PLA₂ groups (cPLA₂, iPLA_2, and sPLA₂) were determined by radioenzymatic assay. Rats fed the high CLA diet had increased hippocampal mRNA levels for specific PLA₂ isoforms (iPla ₂ g6γ; cPla ₂ g4a, sPla ₂ g3, sPla ₂ g1b, and sPla ₂ g12a) and higher enzymatic activity of all PLA₂ groups as compared to those fed the control and the low CLA diet. The increment in PLA₂ activities correlated significantly with memory enhancement, as assessed by increased latency in the step-down inhibitory avoidance task after 4 weeks of treatment (r _s = 0.69 for iPLA₂, P < 0.001; r _s = 0.81 for cPLA₂, P < 0.001; and r _s = 0.69 for sPLA₂, P < 0.001). In face of the previous reports showing reduced PLA₂ activity in AD brains, the present findings suggest that dairy products enriched in cis-9, trans-11 CLA may be useful in the treatment of this disease.