Polyunsaturated fatty acids and cerebral function: Focus on monoaminergic neurotransmission

Abstract

More and more reports in recent years have shown that the intake of polyunsaturated fatty acids (PUFA) constitutes an environmental factor able to act on the central nervous system (CNS) function. We recently demonstrated that the effects of PUFA on behavior can be mediated through effects on the monoaminergic neurotransmission processes. Supporting this proposal, we showed that chronic dietary deficiency in alpha-linolenic acid in rats induces abnormalities in several parameters of the mesocortical and mesolimbic dopaminergic systems. In both systems, the pool of dopamine stored in presynaptic vesicles is strongly decreased. This may be due to a decrease in the number of vesicles. In addition, several other factors of dopaminergic neurotransmission are modified according to the system affected. The mesocortical system seems to be hypofunctional overall [e.g., decreased basal release of dopamine (DA) and reduced levels of dopamine D2 (DAD2) receptors]. In contrast, the mesolimbic system seems to be hyperfunctional overall (e.g., increased basal release of DA and increased levels of DAD2 receptors). These neurochemical changes are in agreement with modifications of behavior already described with this deficiency. The precise mechanisms explaining the effects of PUFA on neurotransmission remain to be clarified. For example, modifications of physical properties of the neuronal membrane, effects on proteins (receptors, transporters) enclosed in the membrane, and effects on gene expression and/or transcription might occur. Whatever the mechanism, it is therefore assumed that interactions exist among PUFA, neurotransmission, and behavior. This might be related to clinical findings. Indeed, deficits in the peripheral amounts of PUFA have been described in subjects suffering from neurological and psychiatric disorders. Involvement of the monoaminergic neurotransmission function has been demonstrated or hypothesized in several of these diseases. It can therefore be proposed that functional links exist among PUFA status, neurotransmission processes, and behavioral disorders in humans. Animal models are tools of choice for the understanding of such links. Improved prevention and complementary treatment of neurological and psychiatric diseases can be expected from these studies.

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

“…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.…”

“…In particular, we showed that the presynaptic dopamine (DA) vesicle compartment was reduced in the frontal cortex of deficient rats, resulting in reduced cortical inhibition in ventral areas, particularly in the nucleus accumbens (13)(14)(15). These neurochemical changes may be responsible for inattention and inefficient reward processing, contributing to learning impairment and to slowing of extinction (16,17). Changes in serotonergic neurotransmission were also reported in rats fed a chronic ALAdeficient diet, and these changes were potentially reversible by an adequate diet, depending on when the intervention occurred (18).…”

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

“…Given the importance of fatty acid/eicosanoid signal transduction in all excitable tissues, it would not be surprising if disturbances in this system were to lead to neurological problems. The balance of dietary -6/ -3 longchain PUFAs may influence levels of neurotransmitters, such as glutamate, acetylcholine (ACh), and dopamine (26)(27)(28)(29)(30), levels of nerve growth factor (31), synaptic membrane function (32,33), the function of membrane proteins (13,18), oxidative stress, lipid peroxidation, antioxidative defense (15,17,(34)(35)(36), glutamate-induced excitotoxicity (37), cerebral blood flow (38,39), ischemic damage (40), blood pressure (41), and cognitive functions (27,33,(42)(43)(44)(45).…”

Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

“…Specifically, previous research has found a reduction in serotonin levels [9], [10], increased concentrations of GABA in the hippocampus [11], a reduction in cholinergic cell numbers [12], increased levels of acetylcholinesterase (AChE) in the hippocampus [13], and a decrease in dopamine segregation in the hypothalamus, hippocampus, and cerebral cortex, all areas related to memory and learning [14], [15].…”