From the Director, Professor Michael Crawford, PhD, FSB, FRCPath.



the director's UPDATE

NEW STRIKING DATA SHOWING THAT PRENATALLY BRAIN DEVELOPMENT IS RESPONSIVE TO DIFFERENT NUTRITIONAL STIMULI IN THE BOYS COMPARED TO THE GIRLS.

  Introduction: The brain is a lipid rich organ with the majority of the adult number of brain cells dividing before birth. It uses arachidonic, adrenic and docosahexaenoic fatty acids in a strongly conserved profile amongst all mammals studied. There are however, differences in the composition of different regions of the brain.

Methods: In a study of lipid status in pregnancy , 86 were recruited to take a supplement with 300 mg of docosahexaenoic acid , 42 mg of eicosapentaenoic acid, 8.4 mg of arachidonic (ArA) and 15mg gamma-linolenic acid with a placebo of olive oil (Vifor Pharma Switzerland), Where possible, magnetic resonance images were obtained of the brains shortly after birth as described previously (i). Red blood cell fatty acids were analysed at recruitment (ca 12 weeks post conception), at delivery and in maternal and fetal cord blood;

Results Data from the placebo group of girls revealed correlations with fatty acids and brain development more related to arachidonic acid rather than DHA or omega 3. In the girls, the proportion linoleic acid (LA) rose whilst ArA fell from recruitment to delivery. The placenta is stealing ArA from the mother for the fetus and at the same time the fetus is rejecting linoleic acid so the ArA falls with time and the LA increases in the maternal blood. The LA/ArA ratio reflects placental/fetal nourishment. Quantitative MRI analysis of regions of the brain showed the omega 3 rich supplement enhanced brain volume, with and without CSF, cortex, whole grey matter, and corpus callosum but only boys . However, in the girls, the Pearson correlation was strongly significant for LA/ArA for the cortex (0.748 p< 0. 004), deep grey matter (0.659 p< 0.014), whole grey matter (0.753 p< 0.003), hippocampus (0.611 p< 0.03), lentiform (0.774 p< 0.002), thalami (0.654 p< 0.015) ,corpus callosum (0.640 p< 0.018), brain (0.685 p< 0.0098), brain with CSF (0.774 p< 0.0019 n=12). ). In addition stearic and nervonic acids had coefficients > 0.59 p<0.001 for cortex, grey matter, corpus callosum, the whole brain with and without CSF. None of these correlates were seen in the placebo boys.

Reference: Ogundipe, E; Tusor N; Wang, Y; Johnson MR; Edwards AD; Crawford MA. (2018) Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their new-born infants PLEFA FOSS trial – ISRCTN 240687; on line ahead of print DOI: https://doi.org/10.1016/j.plefa.2018.09.001

Summary: In this paper we put forward a novel thesis that lipids and the cell membrane bi-layer were the drivers of multi-cellular evolution which led to the Cambrian Explosion of the 32 phyla we have today. Currently, all such matters are interpreted in the context of DNA and proteins. However, DNA had its chance and basically did little or nothing over the first 3 billion years of life on the planet. During that long period there is no intracellular detail seen in the fossil record. It appears in the presence of the raised oxygen tension which allowed the evolution of airbreathing life.

LIPIDS WERE RESPONIBLE FOR THE EVOLUTION OF INTRACELLULAR DETAIL AND MULTI-CELLULAR LIF 500-600 MILLION YEARS AGO:

Summary: When oxygen became available in sufficient amounts in the Cambrian era, Nature could make unsaturated and highly unsaturated fatty acids. For example, the formation of docosahexaenoic acid ( DHA) with six double bonds requires 6 oxygen atoms just to remove the hydrogens. Not easy in an anaerobic condition. Synthesis of fats requires more than twice the amount of energy compared to proteins and carbohydrates. Again not so easy to make fats in the first anaerobic existence. Fats as the phospholipids used in to make the cell membrane, naturally form micelles in water so here, for the first time, Nature was able to wrap up specific functions in specialised compartments. We see special functions such and DNA inside a nuclear envelope, channels for protein synthesis, lysosomes for enzyme storage and mitochondria for energy production. This intracellular specialisation was and is fashioned by the lipid bi-layer membranes. We know today that lipid composition varies with temperature, pressure and chemistry. Membrane lipids are made with various water-soluble head groups such as choline, serine etc and phosphate with the water insoluble aspect made with fatty acids in the middle. There are over 1,000 different combinations making up the individual molecules which are the components of the membrane. We know today that there is selectivity for incorporation of different proteins depending in lipid composition. These proteins include transporters, signallers, ion channels, identifiers etc. Hence Nature had a huge repertoire of lipids and their proteins, to choose from depending on the varying environmental conditions.

The principle of intracellular specialisation can readily be extended to cell specialisation, multi-cellular life and then to speciation: - hence the 32 phyla we have today. Conclusion: It was the lipids rather than the DNA or proteins which was responsible for the origin of multi-cellular life and speciation, in the presence of oxygen during the Cambrian Explosion of the 32 phyla we have today. This has profound implications to present day food and nutrition policies which are dominated by protein. This is especially so since it is the brain which makes us different from other animals and the brain is a lipid rich organ.

Reference: Crawford MA, Schmidt WF, Broadhurst Leigh C, Wang Y. Lipids in the origin of intracellular detail and speciation in the Cambrian epoch and the significance of the last double bond of docosahexaenoic acid in cell signaling. (2021). Prostaglandins, Leukotrienes and Essential Fatty Acids 166 (2021) 102230. https://doi.org/10.1016/j.plefa.2020.102230. MATERNAL NUTRITION AND PREVENTION OF PRETERM BIRTH:

Our study of 296 pregnancies has provided clear evidence that it is the nutrition and health of the mother in the weeks prior to and around the time of conception which matters most to the successful completion of pregnancy to term. In 296 pregnancies the data on red blood cell membrane oleic acid was found to be a powerful predictor of preterm birth at 34 weeks (receiver operator characteristic – ROC – 0.926 p<0.000 n= 296.). The data on the red cell is basically that of its plasma membrane as the cell has no intra cellular organelles. Hence it reflects maternal lipid nutritional status and also of similar maternal plasma membranes as for example that of the endothelium which lines the arteries. With a life span of 120 days and the samples were taken about 12 weeks after conception, this data is telling us that it is maternal nutrition and health in the weeks if not months prior to conception which really matters to the successful completion of pregnancy.

Reference: Ogundipe E, Johnson M, Wang Y, Crawford MA (2016) Peri-conception maternal lipid profiles predict pregnancy outcomes, PLEFA, 114, 35–43. http://dx.doi.org/10.1016/j.plefa.2016.08.012

SEE ALSO- IMPORTANCE OF FISH AND SEA FOOD FOR PREGNANCY Hibbeln JR, Spiller P, Brenna JT, Golding J, Holub BJ, Harris WS, Kris-Etherton P, Lands B, Connor SL, Myers G, Strain JJ, Crawford MA, Carlson SE. (2019) Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews. Prostaglandins Leukot Essent Fatty Acids. 2019 Dec;151:14-36. doi: 10.1016/j.plefa.2019.10.002. PMID: 31739098. Spiller P, Hibbeln JR, Myers G, Vannice G, Golding J, Crawford MA, Strain JJ, Connor SL, Brenna JT, Kris-Etherton P, Holub BJ, Harris WS, Lands B, McNamara RK, Tlusty MF, Salem N Jr, Carlson SE.(2019) An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development. Prostaglandins Leukot Essent Fatty Acids. 2019 Dec;151:8-13. doi: 10.1016/j.plefa.2019.10.001. PMID: 31669935.

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