Biology subjects

Medawar, E.

Publications and source records attributed to Medawar, E..

4 recordsLinked to original sources

bioRxiv2021

Dietary and serum tyrosine, white matter microstructure and inter-individual variability in executive functions in overweight adults: relation to sex/gender and age

Tyrosine (tyr), the precursor of the neurotransmitter dopamine, is known to modulate cognitive functions including executive attention. Tyr supplementation is suggested to influence dopamine-modulated cognitive performance. However, results are inconclusive, regarding the presence or strength and also the direction of the association between tyr and cognitive function. This pre-registered cross-sectional analysis investigates whether diet-associated serum tyr relates to executive attention performance, and whether this relationship is moderated by differences in white matter microstructure. 59 healthy, overweight, young to middle-aged adults (20F, 28.3 {+/-} 6.6 years, BMI: 27.3 {+/-} 1.5 kg/m2) drawn from a longitudinal study reported dietary habits, donated blood and completed diffusion-weighted brain magnetic resonance imaging and the attention network test. Main analyses were performed using linear regressions and non-parametric voxel-wise inference testing. Confirmatory analyses did neither support an association between dietary and serum tyr nor a relationship between relative serum tyr/large neutral amino acids (LNAA) levels or white matter microstructure and executive attention performance. However, exploratory analyses revealed higher tyr intake, higher serum tyr and better executive attention performance in the male sex/gender group. In addition, older age was associated with higher dietary tyr intake and lower fractional anisotropy in a widespread cluster across the brain. Finally, a positive association between relative serum tyr/LNAA and executive attention performance was found in the male sex/gender group when accounting for age effects. Our analysis advances the field of dopamine-modulated cognitive functions by revealing sex/gender and age differences which might be diet-related. Longitudinal or intervention studies and larger sample sizes are needed to provide more reliable evidence for links between tyr and executive attention.

neuroscience↗

bioRxiv2020

Estimating the effect of a scanner upgrade on measures of grey matter structure for longitudinal designs

1Longitudinal imaging studies are crucial for advancing the understanding of brain development over the lifespan. Thus, more and more studies acquire imaging data at multiple time points or with long follow-up intervals. In these studies changes to magnetic resonance imaging (MRI) scanners often become inevitable which may decrease the reliability of the MRI assessments and introduce biases. We therefore investigated the difference between MRI scanners with subsequent versions (3 Tesla Siemens Verio vs. Skyra fit) on the cortical and subcortical measures of grey matter in 116 healthy, young adults using the well-established longitudinal FreeSurfer stream for T1-weighted brain images. We found excellent between-scanner reliability for cortical and subcortical measures of grey matter structure (intra-class correlation coefficient > 0.8). Yet, paired t-tests revealed statistically significant differences in at least 75% of the regions, with percent differences up to 5%, depending on the outcome measure. Offline correction for gradient distortions only slightly reduced these biases. Further, T1-imaging based quality measures systematically differed between scanners. We conclude that scanner upgrades during a longitudinal study introduce bias in measures of cortical and subcortical grey matter structure. Therefore, before upgrading a MRI scanner during an ongoing study, researchers should prepare to implement an appropriate correction method for these effects.

neuroscience↗

bioRxiv2020

Lower intake of animal-based products links to improved weight status, independent of depressive symptoms and personality in the general population

BackgroundRestricting animal-based products from diet may exert beneficial effects on weight status, however whether this is also true for emotional health is unclear. Moreover, differential personality traits may underlie restrictive eating habits and therefore potentially confound diet-health associations. To systematically assess whether restrictive dietary intake of animal-based products relates to lower weight and higher depressive symptoms, and how this is linked to personality traits in the general population. MethodsCross-sectional data was taken from the baseline LIFE-Adult study collected from 2011-2014 in Leipzig, Germany (n = 8943). Main outcomes of interest were 12-month dietary frequency of animal-derived products measured using a Food Frequency Questionnaire (FFQ), body mass index (BMI) (kg/m2), and the Center of Epidemiological Studies Depression Scale (CES-D). Personality traits were assessed in a subsample of n = 7906 using the Five Factor Inventory (NEO-FFI). FindingsHigher restriction of animal-based product intake was associated with a lower BMI (age-, sex- and education-adjusted, n = 8943; {beta} = -.07, p < .001), but not depression score. Personality, i.e. lower extraversion (F (1,7897) = 9.8, p = .002), was related to frequency of animal product intake. Further, not diet but personality was significantly associated with depression, i.e. higher neuroticism ({beta} = .024), lower extraversion ({beta} = -.006), lower agreeableness ({beta} = -.001), lower conscientiousness ({beta} = -.007) and higher BMI ({beta} = .004) (all p < .001, overall model, R2 = .21). The beneficial association with lower weight seemed to be driven by the frequency of meat product intake and not secondary animal products. Likewise, the overall number of excluded food items from the individual diet was associated with a lower BMI (age-, sex- and education-adjusted, n = 8938, {beta} = -.15, p < .001) and additionally with lower depression scores ({beta} = -.004, t = -4.1, p < .001, R2 = .05, corrected for age, sex and education), also when additionally correcting for differences in personality traits ({beta} = -.003, t = -2.7, p = .007, R2 = .21). InterpretationHigher restriction of animal-based products in the diet was significantly associated with a lower BMI, but not with depressive symptoms scores in a large well-characterized population-based sample of adults. In addition, we found that certain personality traits related to restricting animal-based products - and that those traits, but not dietary habits, explained a considerable amount of variance in depressive symptoms. Upcoming longitudinal studies need to confirm these findings and to test the hypothesis if restricting animal-based products, esp. primary animal products ((processed) meat, wurst), conveys benefits on weights status, hinting to a beneficial relationship of animal-based restricted diets in regard to prevention and treatment of overweight and obesity. FundingWe thank all study participants. We very much appreciate the help of the physicians who performed the clinical examinations and data collection, in particular Ulrike Scharrer, Annett Wiedemann, Kerstin Wirkner and her team. This work was supported by LIFE--Leipzig Research Centre for Civilisation Diseases, University of Leipzig. LIFE is funded by means of the European Union, by means of the European Social Fund (ESF), by the European Regional Development Fund (ERDF), and by means of the Free State of Saxony within the framework of the excellence initiative. This work was supported by a scholarship (EM) by the German Federal Environmental Foundation and by the grants of the German Research Foundation contract grant number CRC 1052 "Obesity mechanisms" Project A1 (AV) and WI 3342/3-1 (AVW). The corresponding author had full access to all the data in the included in the analysis and had final responsibility for the decision to submit for publication. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=146 HEIGHT=200 SRC="FIGDIR/small/940460v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1f81d8org.highwire.dtl.DTLVardef@85bd35org.highwire.dtl.DTLVardef@48fd83org.highwire.dtl.DTLVardef@1fbc053_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Effects of rising amyloidβ on hippocampal synaptic transmission, microglial response and cognition in APPSwe/PSEN1M146V transgenic mice

BackgroundProgression of Alzheimers disease is thought initially to depend on rising amyloid{beta} and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloid{beta}, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes.\n\nMethodsCA1 Synaptic transmission and plasticity were investigated using in vitro electrophysiology. Migroglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze.\n\nFindingsThe most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours.\n\nInterpretationThe pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloid{beta} levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition.\n\nResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is a large body of research examining many aspects of phenotypes associated with mouse models of Alzheimers disease - a PubMed search for the terms Alzheimer* AND mouse returns in excess of 21000 articles. However, there are few systematic articles pulling together pathological, functional (electrophysiological), and behavioural analyses across the life-span of such models. There is also a number of conflicting outcomes, for example reports of impaired versus enhanced synaptic plasticity; cognitive impairments or not.\n\nRecently, the importance of microglia in Alzheimers disease has come to the fore in human Genome Wide Association Studies (GWAS), with variants of a number of microglial genes identified as risk-factors for developing the disease. Interestingly, we have recently reported that Trem2 and other genes identified as risk-factors in humans are strongly up regulated in close association to plaque development in the mouse model used in this study. Moreover, this previous study predicted two of the most recently identified genes that were identified in GWAS since the publication of our paper.\n\nWe have previously used this model to identify the earliest synaptic changes and shown changes in release of glutamate, the primary excitatory neurotransmitter in the brain, to occur even before plaques are detectable.\n\nAdded value of this studyBy studying this transgenic mouse model of Alzheimers disease, throughout the development of plaques, from prior to detection through to heavy plaque loads, we have been able to identify a clear time course of key phenotypic changes associated with early disease. In particular, this study identifies the very early changes in microglia and can separate the time course of the microglial phenotype. In addition, we detail the changes in synaptic plasticity over time and importantly identify that, like in humans in the absence of Tau tangles or neurodegeneration, considerable synaptic changes can occur and a heavy plaque load without resulting in substantial cognitive loss.\n\nImplications of all the available evidenceOur data indicate that rising amyloid beta prior to detectable plaque deposition results in changes in synaptic function that likely reflects an enhanced physiological effect of amyloid beta. At this stage, microglia proliferate but do not activate. Once plaques begin to appear, microglia migrate to surround the plaque and become phagocytic, likely targeting dystrophic synapses and neurites caused by the cloud of highly-toxic amyloid beta around the plaque. Similarly to humans, who have plaques but no tangles and have yet to develop substantial neurodegeneration, cognitive deficits are not seen, even with a heavy plaque load; behavioural changes are limited to anxiety-like effects.\n\nThis investigation of the parallel time-course of events highlights the probability that, if progression of disease can be reversed or slowed early enough, before Tau tangles and substantial neurodegeneration occur, the symptoms of cognitive decline could be very largely avoided. Moreover, it suggests that the substantial increases in microglia number and upregulation of their specific gene expression in association with plaques, is not associated with cognitive loss and may indeed be protective.

neuroscience↗