Variation H452Y in HTR2A gene affects immediate visual memory

Serotonin and its receptors, including the 5-Hydroxytryptamine Receptor 2A encoded by the HTR2A gene, are important for learning and memory in animals and humans. Polymorphic variation in the HTR2A gene, which encodes the 5-HT2Aserotonin receptor, has previously been shown to associate with some memory traits, in particular effecting delayed verbal memory. In the current study we have examined the HTR2A His452Tyr (H452Y) substitution for association in a cohort of healthy individuals whose memory traits were assessed using a comprehensive battery of memory tests including, but not limited to, measures of prospective and retrospective memory. Although we failed to replicate previous findings of an effect of the polymorphism on delayed verbal memory, we found a significant association between the HTR2A H452Y polymorphism and immediate visual memory, showing that the heterozygous genotype is associated with poorer immediate visual memory, with delayed visual memory unaffected, although, with correction for multiple testing, this no longer passed significance thresholds. No HTR2A Tyr/Tyr individuals were detected in this cohort due to the low minor allele frequency

The genetic basis of human cognition: Intelligence, learning and memory

The complex and highly polygenic traits of intelligence, learning and memory are fundamental functions of neurocognition. Despite improvements in neurogenetics, our knowledge on the genetic architecture of these functions remains poorly understood. This research investigated the contribution of genetic variation to cognitive performance variability in relation to intelligence, learning and memory using a well-defined, healthy and unrelated cohort via a gene-centric and a genome-wide approach. Results of this study validated several previously identified genes, provided new knowledge on various cognitive traits, and identified several novel regions for future studies that may have consequences for managing disorders involving cognitive impairments

The effect of 1 mg folic acid supplementation on clinical outcomes in female migraine with aura patients

Background: Migraine is a common neurovascular condition that may be linked to hyperhomocysteinemia. We have previously provided evidence that reduction of homocysteine with a vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the occurrence of migraine in response to vitamin supplementation with a lower dose of folic acid. Methods: This was a 6\ua0month randomised, double blinded placebo controlled trial of daily vitamin supplementation containing 1\ua0mg of folic acid, 25\ua0mg of Vitamin B and Vitamin B on reduction of homocysteine and the occurrence of migraine in 300 female patients diagnosed with migraine with aura. Results: Vitamin supplementation with 1\ua0mg of folic acid, did not significantly decrease homocysteine levels (P = 0.2). The treatment group did not show a significant decrease in the percentage of participants with high migraine disability, severity or frequency at the end of the 6\ua0month intervention (P > 0.1). Conclusion: 1\ua0mg of folic acid in combination with vitamin B and B is less effective in reducing migraine associated symptoms compared to the previously tested dosage of 2\ua0mg folic acid in combination with 25\ua0mg of vitamin B and 400\ua0μg of vitamin

HSPGs glypican‐1 and glypican‐4 are human neuronal proteins characteristic of different neural phenotypes

Generating neurons from human stem cells has potential for brain damage therapy and neurogenesis modeling, but current efficacy is limited by culture heterogeneity and the lack of markers. We have previously reported the heparan sulfate proteoglycans (HSPGs) glypican-1 (GPC1) and -4 (GPC4) as the markers of lineage-specific human neural stem cells (hNSCs) and mediators of hNSC lineage potential. Here, we further examined phenotypical characteristics and GPC1 and GPC4 during neural differentiation of hNSCs in the presence of two neurogenic growth factors reported to bind to heparan sulfate: brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor-B (PDGF-B). In hNSC neural cultures, GPC1 and GPC4 were expressed along neurites and cell bodies in long-term (40–60 days) neural differentiation cultures demonstrating the areas of differential localization—suggesting potentially different functions. Neural differentiation cultures in the presence of BDNF or PDGF-B generated phenotypically different neural cells with BDNF treatment associated with higher GPC4 versus GPC1 expression, increased heterogeneity, and differential neuron subtype marker expression to PDGF-B cultures. PDGF-B cultures exhibited higher levels of spontaneous activity and reduced heterogeneity over long-term culture associated with decreased GPC4. Untreated neural cultures were highly variable, supporting the use of neuroregulatory growth factors for guided differentiation. Targeted siRNA downregulation of GPC1/4 reduced neural differentiation markers and altered response to exogenous BDNF and PDGF-B. This work confirms GPC1 and GPC4 as regulators of human neural differentiation and supports their use as novel markers of neural cell characterization.</p

BDNF variants may modulate long-term visual memory performance in a healthy cohort

Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory (p-value = 0.003) in a small cohort (n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale-Fourth Edition subtests Visual Reproduction I and II (VR I and II). VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism (p-value = 0.006)) that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus) that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF, and its anti-sense transcript BDNF-AS, in long-term visual memory performance

Investigation of the CADM2 polymorphism rs17518584 in memory and executive functions measures in a cohort of young healthy individuals

The common polymorphism rs17518584, near the cell adhesion molecule 2 gene (CADM2), was previously identified as playing a role in information processing speed in a genome-wide association study of executive functions and processing speed performed in a cohort of non-demented older adults. In this study, we investigated this polymorphism in a younger population cohort 30 years old, median age 19 years), with no known memory or psychiatric disorders, for which we had phenotyped all participants for memory function (n = 514), and a subset of the participants for executive functions (n = 338), using a battery of tests measuring visuo-spatial memory, working memory, verbal memory, and frontal lobe functions (visual scanning, graphomotor speed, and cognitive flexibility). The polymorphism rs17518584 was genotyped by a restriction fragment length polymorphism assay and analysis indicated that the CADM2 polymorphism showed evidence of association with information processing speed as inferred from scores from the Stroop Word, Colour, and Colour Word Tests (p = 0.005, p = 0.04, and p = 0.028, respectively, in a dominant inheritance model), as well as Trail Making Test Part A (p = 0.005 in an additive model). Significant associations of rs17518584 with scores from other tests of memory subtypes were not detected. The findings of this study provide further support for a role of CADM2 in aspects of cognitive function, in particular reading and information processing speed, and suggest that this role extends to younger individuals.</p

A CREB1 gene polymorphism (rs2253206) is associated with prospective memory in a healthy cohort

Prospective memory (PM) is generally defined as remembering to perform intended actions in the future and is important for functioning in daily life. Cyclic adenosine monophosphate (cAMP) responsive element binding protein 1 (CREB1) plays an important role in cognitive functions. In this study, we hypothesized that genetic variation in the CREB1 gene is associated with PM. We genotyped a CREB1 promoter polymorphism rs2253206 and tested it for association with PM in 619 healthy subjects. PM performance was measured using the Prospective and Retrospective Memory Questionnaire (PRMQ), the Comprehensive Assessment of Prospective Memory (CAPM), and the Memory for Intentions Screening Test (MIST). Generalized linear model analysis was conducted for each PM test independently using different inheritance models to identify any associations (p < 0.05). After multiple testing adjustments, a significant association was found between the rs2253206 genotype and PM performance for CAPM instrumental activities of daily living measure (p = 0.016). These results suggest that the rs2253206 polymorphism in the CREB1 gene locus is associated with PM in healthy individuals and contributes to knowledge on the genetics of this particular type of memor