Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus

Abstract

Because brain membranes contain large amounts of docosahexaenoic acid (DHA, 22:6n-3), and as (n-3) PUFA dietary deficiency can lead to impaired attention, learning, and memory performance in rodents, we have examined the influence of an (n-3) PUFA-deprived diet on the central cholinergic neurotransmission system. We have focused on several cholinergic neurochemical parameters in the frontal cortex and hippocampus of rats fed an (n-3) PUFA-deficient diet, compared with rats fed a control diet. The (n-3) PUFA deficiency resulted in changes in the membrane phospholipid compositions of both brain regions, with a dramatic loss (62-77%) of DHA. However, the cholinergic pathway was only modified in the hippocampus and not in the frontal cortex. The basal acetylcholine (ACh) release in the hippocampus of deficient rats was significantly (72%) higher than in controls, whereas the KCl-induced release was lower (34%). The (n-3) PUFA deprivation also caused a 10% reduction in muscarinic receptor binding. In contrast, acetylcholinesterase activity and the vesicular ACh transporter in both brain regions were unchanged. Thus, we evidenced that an (n-3) PUFA-deficient diet can affect cholinergic neurotransmission, probably via changes in the phospholipid PUFA composition.

n-3 Polyunsaturated fatty acid supplementation reverses stress-induced modifications on brain monoamine levels in mice

“…Although this PUFA was present at very low concentrations in cerebral phospholipids, there may be stress-induced consequences on brain membrane properties. The differences in DHA content of cerebral structures observed in unsupplemented nonstressed mice were exacerbated by n-3 PUFA supplementation, illustrating the previously described differences in accretion (9,39,52). Incorporation of DHA in supplemented mice was higher in the frontal cortex than in the striatum and the hippocampus.…”

“…We have previously shown in animal models that chronic diet deficiency in ALA was able to act on the release of monoamines and acetylcholine in brain regions involved in stress-related behavior (mainly the hippocampus and frontal cortex) (15,16,18,39). 5-HT and acetylcholine release was greater in the basal state in the hippocampus but was reduced under neuronal activation in deficient rats.…”

“…Phosphatidylethanolamine (PE) was separated from total lipids on an aminopropyl-bonded silica gel cartridge (BAKERBOND spe TM Amino; Baker, USA) by the method of Alessandri and Goustard-Langelier (38). The fatty acids were methylated with BF3, and the fatty acid methyl esters were analyzed by gas liquid chromatography (Carlo Erba) (39) and identified by comparison with commercial standards of equivalent chain lengths. The results were expressed as mg fatty acids/100 mg total fatty acids (TFAs; wt %).…”

DHA involvement in neurotransmission process

“…We showed that first, at rest, the synaptic release of acetylcholine was increased by 70% in the hippocampus of a-linolenic aciddeficient animals as compared to controls receiving adequate levels of n-3 and n-6 PUFA. But, the maximum KCl-stimulated release was reduced by 30%, associated to a 70% loss of DHA in phospholipid membranes (figure 8) [27]. Secondly, we showed that a supply of 200 mg of DHA/100 g diet is needed to ensure a release of acetylcholine and an incorporation of DHA in the membranes equivalent to those of the control rats ( figure 9) [42].…”

“…This leads to a severe decrease in DHA levels, notably in the phosphatidylethanolamine (PE) of the frontal cortex, with a well-established compensatory substitution by n-6 PUFA (mainly 22:5n-6, DPA), which are normally absent from brain membranes and thus signs the status of deficiency in the rats [27]. However, we showed that the range of variations of DPA and DHA levels following an a-linolenic acid deprivation were not identical in every sub brain regions.…”