The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1753-4887.2006.tb00242.x

Nutrition in Brain Development and Aging: Role of Essential Fatty Acids

Todorovic, Slobodan M. and Christopher J. Lingle. Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents. J. Neurophysiol. 7...

Pharmacological Properties of T-Type Ca2+ Current in Adult Rat Sensory Neurons: Effects of Anticonvulsant and Anesthetic Agents

Phospholipid fatty acid remodeling in mammalian cells.

Publisher Summary This chapter discusses the biochemistry and function of stratum corneum lipids. The study of lipids as a class of chemical constituents of the stratum corneum offers a unique opportunity to investigate the functional specialization of this tissue. The daily rate of epidermal lipid synthesis in man is equal to the lipid content times the daily loss of stratum corneum. Total epidermal lipid constitutes approximately 10–14% of the dry weight of mammalian epidermis. However, by themselves, isolated intercellular lipids possess no water-holding capacity. The ability of the intercellular lipids to form lamellar bilayers, in the absence of phospholipids, is dependent upon the amphipathic properties of ceramides, free fatty acids, cholesterol, and perhaps lesser constituents such as cholesterol sulfate and proteolipids. The lamellar bilayers are stabilized in an aqueous environment by van der Waals interactions and hydrogen bonds. Moreover, recently, it has been suggested that a major component of the stratum corneum is a ceramide, consisting of 30 to 34-carbon chain length, N-acyl, ω-hydroxyacids covalently bound to the cornified envelope. This leaflet may serve as a scaffold for the intercellular bilayers, thereby contributing to both the barrier and the cohesive properties of the stratum corneum.

The biochemistry and function of stratum corneum lipids.

We examined the possibility that the cutaneous permeability barrier regulates epidermal DNA synthesis in two acute and two chronic models of barrier perturbation. In animals treated topically with acetone, DNA synthesis is increased 102%, in tape-stripped animals 127%, in essential fatty acid deficient animals 50%, and in animals chronically treated with topical lovastatin 64%. This linkage between disturbances in barrier function and increased DNA synthesis is further supported by specific and correlative observations: (a) in these disparate models, artificial replacement of the barrier with a water-impermeable membrane inhibits the expected increase in DNA synthesis; (b) the extent of the burst in DNA synthesis is proportional to the degree of barrier abrogation; (c) the inhibition of DNA synthesis by membranes is directly related to the degree of permeability of these occlusive membranes, i.e., the more impermeable the greater the degree of inhibition; (d) topical treatment with lipids that restore barrier function corrects the increase in DNA synthesis; and (e) barrier abrogation with acetone produces an increase in epidermal DNA synthesis without altering bulk protein synthetic rates in contrast to events known to follow injury or cell replacement. Autoradiographic studies show that the increase in DNA synthesis after acetone treatment is limited to the epidermal basal layer. This constellation of findings strongly suggests that cutaneous barrier function is one factor that regulates epidermal DNA synthesis.

/pdf/barrier-function-regulates-epidermal-dna-synthesis-4hyh6b0rwx.pdf

Barrier function regulates epidermal DNA synthesis.

The molecular mechanism of volatile anesthetic action remains unknown. Attempts to elucidate this mechanism have been complicated by the absence of models in which changes in neuronal cellular properties can be correlated with changes in whole animal anesthetic effect. In this study we describe a model where diet-induced alterations in rat brain fatty acid composition are correlated with alterations in volatile anesthetic potency. Rats maintained on a fat-free diet showed significant depletion of arachidonic acid (20:4 omega 6; 5,8,11,14-eicosatetraenoic acid) and docosahexaenoic acid (22:6 omega 3; 4,7,10,13,16,19,-docosahexaenoic acid) in brain, and a corresponding increase in Mead acid (20: 3 omega 9; 5,8,11-eicosatrienoic acid). These fat-deprived rats were significantly more sensitive to all volatile anesthetics tested than were age-controlled rats on a normal diet. Parenteral supplementation of the fat-deprived animals with linolenic acid (18: 3 omega 3, 9,12,15-octadecatrienoic acid) completely reconstituted the docosahexaenoic acid content of brain without affecting anesthetic sensitivity. In contrast, supplementation of the fat-deprived rats with linoleic acid (18: omega 6; 9,12-octadecadienoic acid) caused a dramatic decrease in anesthetic sensitivity, but only a small change in whole brain arachidonate content. Further analysis revealed that linoleate supplementation of fat-deprived animals resulted in a preferential normalization of the arachidonate content of brain phosphatidylinositol as compared with other brain phosphoglycerides. These results demonstrate for the first time a correlation between changes in membrane composition and anesthetic effect, and indicate that the precise fatty acid composition (perhaps in specific phospholipids) of brain is important in the mechanism of volatile anesthetic action.

/pdf/manipulation-of-rat-brain-fatty-acid-composition-alters-21e0ybz2oq.pdf

Manipulation of rat brain fatty acid composition alters volatile anesthetic potency.

A unique cardiac cytosolic acyltransferase with preferential selectivity for fatty acids that form cyclooxygenase/lipoxygenase metabolites and reverse essential fatty acid deficiency

William J. Elliott

Papers

Manipulation of rat brain fatty acid composition alters volatile anesthetic potency.

A unique cardiac cytosolic acyltransferase with preferential selectivity for fatty acids that form cyclooxygenase/lipoxygenase metabolites and reverse essential fatty acid deficiency

Arachidonic acid metabolism by rabbit fetal membranes of various gestational ages

Physiologic effects of columbinic acid and its metabolites on rat skin.

Essential fatty acid deficiency: A new look at an old problem