Increased levels of cytosolic phospholipase A2 in dyslexics

MacDonell, L.E.F.; Skinner, Frank; Ward, P.E.; Glen, A.I.M.; MacDonald, Donald J.; Boyle, R.M.; Horrobin, David F.

doi:10.1054/plef.2000.0189

Cited by 33 publications

(12 citation statements)

References 11 publications

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“…Cerebral P-31 magnetic resonance in dyslexics indicate increased membrane PL turnover [250]. Increased PLA2 activity has also been suggested [251]. Supplementation with PUFA from the omega-3 and omega-6 series (186 mg EPA, 480 mg DHA, 96 mg GLA, 864 mg LA and 42 mg AA per day) improved ADHD symptoms in children with learning disabilities (mainly dyslexia) [160] and supplementation with DHA for 1 month improved dark adaptation in dyslexic young adults [252].…”

Section: Other Disordersmentioning

confidence: 99%

Omega-3 fatty acids and neuropsychiatric disorders

2005

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-Epidemiological evidence suggests that dietary consumption of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for certain neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia and Depression. Supplementation studies, using individual or combination omega-3 fatty acids, suggest the possibility for decreased symptoms associated with some of these conditions. Thus far, however, the benefits of supplementation, in terms of decreasing disease risk and/or aiding in symptom management, are not clear and more research is needed. The reasons for blood fatty acid alterations in these disorders are not known, nor are the potential mechanisms by which omega-3 fatty acids may function in normal neuronal activity and neuropsychiatric disease prevention and/or treatment. It is clear, however, that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor. Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression. This review summarizes the knowledge in terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence pointing to potential mechanisms of omega-3 fatty acids in normal brain functioning, development of neuropsychiatric disorders and efficacy of omega-3 fatty acid supplementation in terms of symptom management.

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Section: Other Disordersmentioning

confidence: 99%

Omega-3 fatty acids and neuropsychiatric disorders

2005

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“…The turnover of these is under the control of phospholipases, in particular PLA2. It has recently been shown that there are increased levels of this enzyme in dyslexics (Macdonnell et al, 2000) which may remove excessive amounts of PUFAs from the membrane and thus compromise rapid channel responses in magnocells. Furthermore, this enzyme may be modulated by the MRC system since immune reactions mobilize PUFAs from cell membranes to provide precursors of the cytokines required for effective cellular responses to foreign material.…”

Section: Polyunsaturated Fatty Acidsmentioning

confidence: 99%

The magnocellular theory of developmental dyslexia

2001

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Low literacy is termed 'developmental dyslexia' when reading is significantly behind that expected from the intelligence quotient (IQ) in the presence of other symptoms--incoordination, left-right confusions, poor sequencing--that characterize it as a neurological syndrome. 5-10% of children, particularly boys, are found to be dyslexic. Reading requires the acquisition of good orthographic skills for recognising the visual form of words which allows one to access their meaning directly. It also requires the development of good phonological skills for sounding out unfamiliar words using knowledge of letter sound conversion rules. In the dyslexic brain, temporoparietal language areas on the two sides are symmetrical without the normal left-sided advantage. Also brain 'warts' (ectopias) are found, particularly clustered round the left temporoparietal language areas. The visual magnocellular system is responsible for timing visual events when reading. It therefore signals any visual motion that occurs if unintended movements lead to images moving off the fovea ('retinal slip'). These signals are then used to bring the eyes back on target. Thus, sensitivity to visual motion seems to help determine how well orthographic skill can develop in both good and bad readers. In dyslexics, the development of the visual magnocellular system is impaired: development of the magnocellular layers of the dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity is reduced; many dyslexics show unsteady binocular fixation; hence poor visual localization, particularly on the left side (left neglect). Dyslexics' binocular instability and visual perceptual instability, therefore, can cause the letters they are trying to read to appear to move around and cross over each other. Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good magnocellular function is essential for high motion sensitivity and stable binocular fixation, hence proper development of orthographic skills. Many dyslexics also have auditory/phonological problems. Distinguishing letter sounds depends on picking up the changes in sound frequency and amplitude that characterize them. Thus, high frequency (FM) and amplitude modulation (AM) sensitivity helps the development of good phonological skill, and low sensitivity impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM is significantly lower than that of good readers and this explains their problems with phonology. The cerebellum is the head ganglion of magnocellular systems; it contributes to binocular fixation and to inner speech for sounding out words, and it is clearly defective in dyslexics. Thus, there is evidence that most reading problems have a fundamental sensorimotor cause. But why do magnocellular systems fail to develop properly? There is a clear genetic basis for impaired development of magnocells throughout the brain. The best understood linkage is to the region of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of chr...

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“…Increased cPla 2 activity might also result in a deficiency of highly unsaturated fatty acids (e.g., arachidonic acid) such as that observed by Richardson et al [2000] in a group of dyslexic children. However, the studies by MacDonell et al [2000] and by Richardson et al [2000] supply only weak evidence of a role for cPla 2 in RD, and no published studies have followed up these findings. Nevertheless, given the scant evidence supporting neurobiological hypotheses of RD, we considered the phospholipase genes mapping to 15q15 to be the only two functional positional candidate genes for RD in this region.…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that increased PAF, a downstream product of arachidonic acid release mediated by cPla 2 , could explain the neuronal abnormalities such as ectopias and microgyria observed by some in the brains of RD individuals [Taylor et al, 2001]. MacDonell et al [2000] have reported higher levels of cPla 2 in the blood of dyslexic adults compared with controls. Increased cPla 2 activity might also result in a deficiency of highly unsaturated fatty acids (e.g., arachidonic acid) such as that observed by Richardson et al [2000] in a group of dyslexic children.…”

Section: Introductionmentioning

confidence: 99%

Association analysis of two candidate phospholipase genes that map to the chromosome 15q15.1‐15.3 region associated with reading disability

Morris

Ivanov

Robinson

et al. 2004

American J of Med Genetics Pt B

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Molecular genetic studies have suggested a reading disability (RD, dyslexia) susceptibility locus on chromosome 15q. We have previously mapped this locus by association to the region surrounding D15S994. Very little is known about the neurobiological processes involved in RD, and therefore selecting positional candidate genes for analysis based upon function is difficult. Nevertheless we were able to identify two functional candidates based upon existing hypotheses. Both were phospholipase genes, phospholipase C beta 2 (PLCB2) and phospholipase A2, group IVB (cytosolic; PLA2G4B). D15S944 is located within PLCB2 and is 1.6 Mb from PLA2G4B. We examined each gene for association using a mixed direct and indirect association approach, a case (n = 164)/control (n = 174) sample, and a partially overlapping sample of 178 RD parent-proband trios from South Wales and England. Mutation analysis revealed 14 sequence variants in PLCB2 and 33 variants in PLA2G4B. All non-synonymous SNPs were genotyped as were SNPs across each gene with maximum distance between SNPs of 6 kb. Case-control analyses revealed modest evidence (0.01 < P < 0.05) for association between a single variant in PLCB2 and two variants in PLA2G4B. However, association was not confirmed in the family based sample. As the latter sample has previously generated replicated significant evidence for association between RD and markers/haplotypes surrounding D15S944, it should have sufficient power to detect association to variants in susceptibility gene itself. We conclude that neither gene accounts for the association signal we previously observed. As these are the only clear cut functional candidate genes in the region, identification of the putative susceptibility locus for RD on 15q will require more methodical non-hypothesis driven positional cloning approaches.

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Increased levels of cytosolic phospholipase A2 in dyslexics

Cited by 33 publications

References 11 publications

Omega-3 fatty acids and neuropsychiatric disorders

Omega-3 fatty acids and neuropsychiatric disorders

The magnocellular theory of developmental dyslexia

Association analysis of two candidate phospholipase genes that map to the chromosome 15q15.1‐15.3 region associated with reading disability

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