Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects

Skinner, E. R.; Watt, Carolyn; Besson, J. A. O.; Best, P. V.

doi:10.1093/brain/116.3.717

Cited by 126 publications

(81 citation statements)

References 31 publications

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“…Only a single study has examined the EC for changes in its phospholipids in AD, finding no changes in either total PC, PE or PS (Chan et al 2012). Two further studies examined the parahippocampal gyrus (Skinner et al 1993;Prasad et al 1998), but only Prasad et al (1998) observed a loss of DHA with AD within the PE class of phospholipids. Although the current evidence is relatively sparse, if the loss of PE-DHA in the EC and greater parahippocampal gyrus is indeed involved in the progression of AD, then the increase in PE-DHA during normal aging could be protective against further development of AD neuropathology; however, much work remains to be done to explore this theory.…”

Section: Discussionmentioning

confidence: 99%

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The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

et al. 2017

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Membrane lipid composition is altered in the brain during the pathogenesis of several age-related neurodegenerative diseases, including Alzheimer's disease. The entorhinal cortex is one of the first regions of the brain to display the neuropathology typical of Alzheimer's disease, yet little is known about the changes that occur in membrane lipids within this brain region during normal aging (i.e., in the absence of dementia). In the present study, the phospholipid composition of mitochondrial and microsomal membranes from human entorhinal cortex was examined for any changes over the adult lifespan (18-98 years). Overall, changes in several molecular phospholipids were seen with age in the entorhinal cortex across both membranes. The proportion of total phosphatidylcholine within the mitochondrial fraction increased within the entorhinal cortex with age, while total mitochondrial phosphatidylethanolamine decreased. Many mitochondrial phosphatidylethanolamines containing docosahexaenoic acid increased with age; however, this did not translate into an overall age-related increase in total mitochondrial docosahexaenoic acid. The most abundant phospholipid present within the human brain, PC 16:0_18:1, also increased with age within the mitochondrial membranes of the entorhinal cortex. When compared to other regions of the brain, the phospholipid composition of the entorhinal cortex remains relatively stable in adults over the lifespan in the absence of dementia.

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Section: Discussionmentioning

confidence: 99%

“…In respect to phospholipids, Chan et al (2012) observed numerous changes to phospholipid species in the EC with AD. Changes to the phospholipid composition of the entire parahippocampal gyrus with AD have also been reported, with alterations in several polyunsaturated fatty acids being observed (Skinner et al 1993;Prasad et al 1998).…”

Section: Introductionmentioning

confidence: 94%

The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

et al. 2017

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“…1 is estimated to account for ϳ30% of the total fatty acids in brain tissue aminophospholipids (1,2). DHA is believed to be important for brain development (3), and its deficiency is associated with abnormalities in brain function (4).…”

Section: Docosahexaenoic Acid (C22:63 Dha)mentioning

confidence: 99%

Formation of Highly Reactive A-ring and J-ring Isoprostane-like Compounds (A4/J4-neuroprostanes) in Vivo from Docosahexaenoic Acid

Fam

Murphey

Terry

et al. 2002

Journal of Biological Chemistry

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Free radical-initiated oxidant injury and lipid peroxidation have been implicated in a number of neural disorders. Docosahexaenoic acid is the most abundant unsaturated fatty acid in the central nervous system. We have shown previously that this 22-carbon fatty acid can yield, upon oxidation, isoprostane-like compounds termed neuroprostanes, with E/D-type prostane rings (E 4 /D 4 -neuroprostanes). Eicosanoids with E/D-type prostane rings are unstable and dehydrate to cyclopentenone-containing compounds possessing A-type and J-type prostane rings, respectively. We thus explored whether cyclopentenone neuroprostanes (A 4 /J 4 -neuroprostanes) are formed from the dehydration of E 4 /D 4 -neuroprostanes. Indeed, oxidation of docosahexaenoic acid in vitro increased levels of putative A 4 /J 4 -neuroprostanes 64-fold from 88 ؎ 43 to 5463 ؎ 2579 ng/mg docosahexaenoic acid. Chemical approaches and liquid chromatography/electrospray ionization tandem mass spectrometry definitively identified them as A 4 /J 4 -neuroprostanes. We subsequently showed these compounds are formed in significant amounts from a biological source, rat brain synaptosomes. A 4 /J 4 -neuroprostanes increased 13-fold, from a basal level of 89 ؎ 72 ng/mg protein to 1187 ؎ 217 ng/mg (n ‫؍‬ 4), upon oxidation. We also detected these compounds in very large amounts in fresh brain tissue from rats at levels of 97 ؎ 25 ng/g brain tissue (n ‫؍‬ 3) and from humans at levels of 98 ؎ 26 ng/g brain tissue (n ‫؍‬ 5), quantities that are nearly an order of magnitude higher than other classes of neuroprostanes. Because of the fact that A 4 /J 4 -neuroprostanes contain highly reactive cyclopentenone ring structures, it would be predicted that they readily undergo Michael addition with glutathione and adduct covalently to proteins. Indeed, incubation of A 4 /J 4 -neuroprostanes in vitro with excess glutathione resulted in the formation of large amounts of adducts. Thus, these studies have identified novel, highly reactive A/J-ring isoprostanelike compounds that are derived from docosahexaenoic acid in vivo.

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“…The binding of cationic drugs to anionic lipids may be higher than to such zwitterionic polar lipids as phosphatidylcholine, phosphatidylethanolamine or sphingomyelin. Moreover, dierences in the fatty acid composition of the grey and white matter may also be of importance for the binding of the investigated psychotropic drugs (Skinner et al, 1993).…”

mentioning

confidence: 99%

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

Daniel

Wójcikowski

Pałucha

2001

British J Pharmacology

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1 Since the brain is not a homogenous organ (i.e. the phospholipid pattern and density of lysosomes may vary in its dierent regions), in the present study we examined the uptake of psychotropic drugs by vertically cut slices of whole brain, grey (cerebral cortex) and white (corpus callosum, internal capsule) matter of the brain and by neuronal and astroglial cell cultures. 2 Moreover, we assessed the contribution of lysosomal trapping to total drug uptake (total uptake=lysosomal trapping+phospholipid binding) by tissue slices or cells conducting experiments in the presence and absence of`lysosomal inhibitors', i.e., the lysosomotropic compound ammonium chloride (20 mM) or the Na + /H + -ionophore monensin (10 mM), which elevated the internal pH of lysosomes. The initial concentration of psychotropic drug in the incubation medium was 5 mM. 3 Both total uptake and lysosomal trapping of the antidepressants investigated (imipramine, amitriptyline,¯uoxetine, sertraline) and neuroleptics (promazine, perazine, thioridazine) were higher in the grey matter and neurones than in the white matter and astrocytes, respectively. Lysosomal trapping of the psychotropics occurred mainly in neurones where thioridazine sertraline and perazine showed the highest degree of lysosomotropism. 4 Distribution interactions between antidepressants and neuroleptics took place in neurones via mutual inhibition of lysosomal trapping of drugs. 5 A dierential number of neuronal and glial cells in the brain may mask the lysosomal trapping and the distribution interactions of less potent lysosomotropic drugs in vertically cut brain slices. 6 A reduction (via a distribution interaction) in the concentration of psychotropics in lysosomes (depot), which leads to an increase in their level in membranes and tissue¯uids, may intensify the pharmacological action of the combined drugs.

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Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects

Cited by 126 publications

References 31 publications

The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

Formation of Highly Reactive A-ring and J-ring Isoprostane-like Compounds (A4/J4-neuroprostanes) in Vivo from Docosahexaenoic Acid

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

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