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, iPLA2, 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 (rs = 0.69 for iPLA2, P < 0.001; rs = 0.81 for cPLA2, P < 0.001; and rs = 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.
Embrapa Dairy Cattle, Brazilian Agricultural Research Corporation, Juiz de Fora, Minas Gerais, Brazil.
Marco A S
MA
Gama
Faculty of Pharmacy, Research Center for Innovative Health Sciences, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil.
Nádia R B
NR
Raposo
Laboratory of Neurosciences-LIM27, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Fábio B
FB
Mury
Embrapa Dairy Cattle, Brazilian Agricultural Research Corporation, Juiz de Fora, Minas Gerais, Brazil.
Fernando C F
FC
Lopes
Laboratory of Neurosciences-LIM27, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Emmanuel
E
Dias-Neto
Laboratory of Neurosciences-LIM27, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Leda L
LL
Talib
Laboratory of Neurosciences-LIM27, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. gattaz@usp.br.
Wagner F
WF
Gattaz
D000544:Alzheimer Disease / Q000178:diet therapy; D000821:Animal Feed; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D002079:Butter; D004032:Diet; D006624:Hippocampus / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated; D008297:Male; D008568:Memory / Q000502:physiology*; D054467:Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011581:Psychological Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D017208:Rats, Wistar; D015854:Up-Regulation
D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D002079:Butter; D054467:Phospholipases A2
Alzheimer disease; Brain tissue; Conjugated linoleic acid; Dairy fat; Immunomodulation; Phospholipase A2