ABSTRACT
BACKGROUND: Anatomic and functional brain lateralization underlies hemisphere specialization for cognitive and motor control, and deviations from the normal patterns of asymmetry appear to be related to behavioral deficits. Studies on n-3 polyunsaturated fatty acid (PUFA) deficiency and behavioral impairments led us to postulate that a chronic lack of n-3 PUFA can lead to changes in lateralized behavior by affecting structural or neurochemical patterns of asymmetry in motor-related brain structures. METHODS: We compared the effects of a chronic n-3 PUFA deficient diet with a balanced diet on membrane phospholipid fatty acids composition and immunolabeling of choline acetyltransferase (ChAt), as a marker of cholinergic neurons, in left and right striatum of rats. Lateral motor behavior was assessed by rotation and paw preference. RESULTS: Control rats had an asymmetric PUFA distribution with a right behavioral preference, whereas ChAt density was symmetrical. In deficient rats, the cholinergic neuron density was 30% lower on the right side, associated with a loss of PUFA asymmetry and behavior laterality. They present higher rotation behavior, and significantly more of them failed the handedness test. CONCLUSION: These results indicate that a lack of n-3 PUFA is linked with a lateral behavior deficit, possibly leading to cognitive disturbances.
Subject(s)
Behavior, Animal/physiology , Corpus Striatum/physiology , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-3/physiology , Fatty Acids, Unsaturated/deficiency , Functional Laterality/physiology , Acetylcholine/metabolism , Acetylcholine/physiology , Animals , Choline O-Acetyltransferase/metabolism , Cognition Disorders/etiology , Corpus Striatum/enzymology , Corpus Striatum/metabolism , Dietary Fats/metabolism , Disease Models, Animal , Fatty Acids, Unsaturated/metabolism , Female , Humans , Immunohistochemistry , Membrane Transport Proteins/metabolism , Motor Activity/physiology , Motor Cortex/enzymology , Motor Cortex/metabolism , Motor Cortex/physiology , Neurons/enzymology , Neurons/metabolism , Neurons/physiology , Rats , Rats, WistarABSTRACT
Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the only treatment--in several psychiatric disorders. The mechanisms by which polyunsaturated fatty acids have an impact on neuronal functions will be reviewed: the modulation of membrane biophysical properties, regulation of neurotransmitter release, synthesis of biologically active oxygenated derivatives, and nuclear receptor-mediated transcription of genes responsive to fatty acids or to their derivatives.
Subject(s)
Central Nervous System/physiology , Dietary Fats, Unsaturated/metabolism , Fatty Acids, Unsaturated/physiology , Visual Acuity/drug effects , Adolescent , Adult , Aged , Animals , Arachidonic Acid/administration & dosage , Arachidonic Acid/metabolism , Brain/metabolism , Brain/physiology , Central Nervous System/metabolism , Child , Child, Preschool , Dietary Fats, Unsaturated/administration & dosage , Docosahexaenoic Acids/administration & dosage , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid/administration & dosage , Eicosapentaenoic Acid/metabolism , Eicosapentaenoic Acid/physiology , Fatty Acids, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/metabolism , Female , Food, Fortified , Humans , Infant , Infant Formula/chemistry , Infant Formula/standards , Infant, Newborn , Male , Middle Aged , Milk, Human/chemistry , Milk, Human/physiology , Nutritional Requirements , Pregnancy , Visual Acuity/physiologyABSTRACT
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.
