Omega-3 fatty acids deprivation affects ontogeny of glutamatergic synapses in rats: Relevance for behavior alterations

Abstract

Essential omega-3 polyunsaturated fatty acids (omega3) are crucial to brain development and function, being relevant for behavioral performance. In the present study we examined the influence of dietary omega3 in the development of the glutamatergic system and on behavior parameters in rats. Female rats received isocaloric diets, either with omega3 (omega3 group) or a omega3 deficient diet (D group). In ontogeny experiments of their litters, hippocampal immunocontent of ionotropic NMDA and AMPA glutamatergic receptors subunits (NR2 A\B and GluR1, respectively) and the alpha isoform of the calcium-calmodulin protein kinase type II (alphaCaMKII) were evaluated. Additionally, hippocampal [(3)H]glutamate binding and uptake were assessed. Behavioral performance was evaluated when the litters were adult (60 days old), through the open-field, plus-maze, inhibitory avoidance and flinch-jump tasks. The D group showed decreased immunocontent of all proteins analyzed at 02 days of life (P2) in comparison with the omega3 group, although the difference disappeared at 21 days of life (except for alphaCaMKII, which content normalized at 60 days old). The same pattern was found for [(3)H]glutamate binding, whereas [(3)H]glutamate uptake was not affected. The D group also showed memory deficits in the inhibitory avoidance, increased in the exploratory pattern in open-field, and anxiety-like behavior in plus-maze. Taken together, our results suggest that dietary omega3 content is relevant for glutamatergic system development and for behavioral performance in adulthood. The putative correlation among the neurochemical and behavioral alterations caused by dietary omega3 deficiency is discussed.

Dietary omega-3 deficiency reduces BDNF content and activation NMDA receptor and Fyn in dorsal hippocampus: Implications on persistence of long-term memory in rats

“…8 To evaluate the influence of n-3 fatty acids in the diet and to manage the n-3 fatty acids in the maternal milk supply, female rats were divided into two groups 2 weeks before mating: the n-3 diet group (ω3) and the n-3 deficient diet group (D). Female Wistar rats were housed in an air-conditioned room (21-22°C) with a 12 hours dark-light cycle, and food and water were offered ad libitum.…”

“…12 We previously demonstrated that n-3 deficient rats showed memory deficits, as well as impaired performance in inhibitory avoidance compared with animals that received an adequate n-3 diet. 8 The persistence of long-term memory (LTM, measured 7 days after the inhibitory avoidance training session) in n-3 deficient rats was diminished compared with the n-3 adequate group. 8 The acquisition of memory is a process involving molecular and cellular events that occur early after a training session and last from several hours to a few days in specific brain regions, such as the hippocampus.…”

“…8 The persistence of long-term memory (LTM, measured 7 days after the inhibitory avoidance training session) in n-3 deficient rats was diminished compared with the n-3 adequate group. 8 The acquisition of memory is a process involving molecular and cellular events that occur early after a training session and last from several hours to a few days in specific brain regions, such as the hippocampus. 13,14 The molecular events that influence memory formation in the hippocampus involve the activation of N-methyl-D-aspartate (NMDA) glutamate receptors and downstream signaling cascades, which are important for the induction of longterm potentiation (LTP) and synthesis of brain derived neurotrophic factor (BDNF).…”

“…[4][5][6] It was postulated that an insufficient dietary supply of n-3 PUFAs during pre-and postnatal development decreases the levels of DHA in neural tissue. The decrease in DHA was accompanied by a reciprocal increase in docosapentaenoic acid (DPA, C22:5 n-6), 7 which led to behavioral deficits in animal models, [8][9][10] especially deficits in memory performance. 8,10,11 Accordingly, the recovery of brain DHA levels restores memory performance.…”

“…The decrease in DHA was accompanied by a reciprocal increase in docosapentaenoic acid (DPA, C22:5 n-6), 7 which led to behavioral deficits in animal models, [8][9][10] especially deficits in memory performance. 8,10,11 Accordingly, the recovery of brain DHA levels restores memory performance. 12 We previously demonstrated that n-3 deficient rats showed memory deficits, as well as impaired performance in inhibitory avoidance compared with animals that received an adequate n-3 diet.…”