Effects of a n-3 PUFA deficient diet on the expression of retinoid nuclear receptors, neurogranin and neuromodulin in rat brain

Benjamin Buaud,Véronique Pallet,Carole Boue,Paul Higueret,Nicole Combe

doi:10.1051/ocl.2007.0117

Abstract

A lot of studies performed in rodents revealed that n-3 polyunsaturated fatty acid (PUFA) deficient diets could induce deficits of learning capacities but the mechanisms involved are not well known. Retinoic acid (RA) and its nuclear receptors (RAR and RXR) play a central role in the maintenance of cognitive processes and synaptic plasticity via its action on target genes that are neurogranin (RC3) and neuromodulin (GAP43). Given some interferences were described between the retinoid and fatty acid signaling pathways, we investigated the effects of a _α-linolenic acid (18: 3 n-3) deficient diet on retinoic acid nuclear receptors (RAR, and RXR), on GAP43 and RC3, and on blood and brain fatty acid composition in rats at three times of diet: 3, 9 and 18 weeks. In blood and brain of these animals, we observed a severe n-3 PUFA deficit (18:3 n-3, 20:5 n-3 and particularly 22:6 n-3) associated with an increase in the n-6 PUFA content (mainly 22:5 n-6). Real-time PCR and western blot analysis allowed us to note that retinoid signaling, GAP43 and RC3 expression were affected in the striatum of the n-3 PUFA deprived rats.

Highlights

Retinoic acid (RA) controls, via its nuclear receptors RAR and RXR, the expression of genes involved in synaptic plasticity, memory [10] and cognitive processes [11]
The retinoic acid nuclear receptor expression was studied in the striatum of rats fed the deficient diet for 3, 9 and 18 weeks
Regarding the consequences of such results, if we consider some bibliographic data showing that RC3 knockout mice have impaired synaptic plasticity and spatial learning [24], and as well as that decreased GAP43 expression was associated with reduced neuronal plasticity and learning [25], we can suppose that the n-3 deficiency could lead to similar cognitive alterations

Summary

Introduction

Brain is a tissue rich in lipids (about 5060 percent of its dry weight). Cerebral membranes are especially rich in n-6 and n-3 PUFAs; arachidonic (20:4 n-6, AA) and docosahexaenoic acids (22:6 n-3, DHA) are their main representatives. RA controls, via its nuclear receptors RAR (retinoic acid receptor) and RXR, the expression of genes involved in synaptic plasticity, memory [10] and cognitive processes [11].

Results

Conclusion