Browsing by Person "Ferrington, Linda"

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Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice
(Nature Publishing Group, 2016-06-01) Beglopoulos, V.; Tulloch, J.; Roe, A. D.; Daumas, S.; Ferrington, Linda; Watson, R.; Fan, Z.; Hyman, B. T.; Kelly, P. A. T.; Bard, F.; Morris, R. G. M.
Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-_-amyloid antibody. Our data suggest a biomarker strategy for the early detection of _-amyloid-related abnormalities.
Effect of Vitamin D supplementation on aerobic exercise performance in healthy adults; a randomised single blinded placebo controlled pilot study
(ECronicon, 2016-09-27) Ferrington, Linda; Bell, Steph; Robertson, Amy; Revuelta-Iniesta, Raquel
Background: 1,25-dihydroxyvitamin D (1,25(OH)D), the biologically active form of vitamin D, is thought to be directly related to exercise induced inflammation and skeletal muscle performance and deficiency has catabolic effects on muscle tissue, causes muscle weakness and impairs cross-bridge formation. 1,25(OH)D may also affect cardiovascular risk factors such as blood pressure (BP), which in turn may have an effect on aerobic exercise; however, at present evidence investigating this association are lacking. Therefore,the aim of this study was to investigate the effect of vitamin D supplementation on aerobic exercise following two weeks of intervention. Methods: A randomised placebo controlled single-blinded pilot study aimed to investigate the short term effects of vitamin D supplementation on aerobic exercise performance in a group of healthy adults. Eleven healthy adults were allocated to receive either 2000IU (50_g/day) of vitamin D or a placebo (sucrose) for 14 days. Physical activity and diet diaries were completed throughout the study. Aerobic exercise performance was assessed at baseline and day 14 following a 15-minute run on a treadmill set at a gradient of 1.5%. Height, weight, systolic/diastolic BP and heart rate (HR) were recorded at baseline and day 14 before running. Parameters of aerobic exercise exertion (BP, %HR and difference in blood lactate) were recorded before and after each run. The rate of perceived exertion (RPE) was recorded after each run. Results: HR reduced significantly by 2.5% (p = 0.002) from 91.5 4.5% to 89.0 3.7% in the intervention group, but not in the placebo group (1.2%; 87.8 4.5% to 86.6 5.1%. p = 0.4). The difference in blood lactate between pre and post run was smaller in the intervention group [(3.9 3.7 mmol/L; p = 0.2 SEM (1.5)] than in the placebo group [(5.5 3.8 mmol/L; p = 0.1; SEM (5.9)]; however,this did not statistically differ between [p = 0.5; SEM (2.2)] and within the groups. Finally, a statistically significant reduction [(p = 0.001; SEM (0.7)] in RPE was found in the intervention group only (15.8 1.9 to 14.7 2.2). Conclusion: The significant reduction in both percentage heart rate and rate of perceived exertion found in this study over a two week period suggest that short term vitamin D supplementation may improve aerobic exercise performance. However, larger scale studies are now warranted to verify these findings.
The acute and long-term effects of 3,4- methylenedioxymethamphetamine (MDMA; 'ecstasy') upon cerebral and cerebrovascular serotonergic processes.
(Queen Margaret University, 2004) Ferrington, Linda
The amphetamine derivative 3,4,-methylenedioxymethamphetamine (MDMA; Ecstasy) is a recreational drug of abuse, particularly popular among young people with whom it has formed a well-established sub-culture. MDMA is popular for its euphoria-inducing and mild stimulant properties and its popularity continues to rise despite a number of well-publicised cases of MDMA-associated fatalities and evidence of MDMA-induced acute toxicity. MDMA is known to produce an acute efflux of serotonin (5-HT) release in the brains of experimental animals, in which a marked behavioural response is also demonstrated. In the long-term MDMA causes specific neurotoxic damage to serotonergic nerve terminals, a phenomenon which is not demonstrated in other neurotransmitters. MDMA use has been associated with long-term adverse effects on both psychological and physiological health and this may represent a major public health problem given the 2 million people who use the drug in the UK alone. However, there is a perceived imbalance between the relative number of those who use MDMA and the serious adverse effects of the drug and it is possible that these may occur in a more susceptible sub-population of users. This thesis involves in vivo work using the Dark Agouti (DA) rat strain which is known to be more susceptible to MDMA and which may therefore provide an insight in this more susceptible sub-population of human MDMA users. The data presented in this thesis demonstrate that a single exposure to MDMA (15mg.kg-1) has a significal effect upon local cerebral glucose utilisation (LCMRglu) and local cerebral blood flow (LCBF) in DA rats both acutely and in the longer-term. This work demonstrates that this single dose of MDMA is neurotoxic to serotonergic neurons, inducing up to 80% depletion of serotonergic nerve terminals 6 weeks later. Furthermore, data generated from pharmacological challenges upon animals treated with MDMA 6 weeks earlier demonstrates the existence of compensatory mechanisms which act to normalise LCMRglu and LCBF, despite the persistence of serotonergic depletion. Thus this thesis extends the currently available information regarding acute and long-term effects of MDMA in a vulnerable sub-population of users and also proposes potential theories for the mechanisms of action by which pharmacological compensation for these long-term effects of MDMA-induced neurotoxicity may occur. In addition this thesis examines the effects of previous exposure to MDMA upon physiological challenges that might realistically be encountered by human users of the drug. The nature of MDMA-induced neurotoxicity suggests that human users of MDMA may suffer from untreatable chronic psychosis, and this thesis lends support to the view that currently available first line anti-depressant therapies may not be useful in the treatment of this sub-section of the population.