Book of abstracts - British Neuroscience Association

More documents

Recommendations

Info

50.04 A combined intracranial EEG, MEG and fMRI look at audiovisual speech integration. Calvert G School of Psychology, University of Bath Combining information from the different senses can dramatically improve the detection and discrimination of external stimuli and speed responsiveness. Given the ubiquitous nature of crossmodal processing for human experience, knowledge of the underlying neurophysiology seems vital for a complete understanding of human sensory perception. Modern human brain imaging techniques now provide a means of characterising the neural bases of these intersensory interactions. In our laboratory, we have used a combination of imaging techniques including functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG) and electrocorticography (EcoG) to explore these phenomena. By combining the information obtainable from these different methodologies, in some instances in the same subjects and using the same paradigms, we are beginning to elucidate many of the brain areas involved in multisensory integration and the time course of information flow through these emerging networks. 51.01 Alzheimer’s disease is a world-wide problem:the burden and current standards of care Mohs R Eli Lilly, Indianapolis, USA ABSTRACT NOT RECEIVED 51.02 What is the significance of tau pathology in Alzheimer’s disease Davies P Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461. Changes in the phosphorylation state and the conformation of tau occur early in the development of Alzheimer’s disease. These changes appear to be reliable markers of the neurodegenerative process in this condition, and distinguish the process of Alzheimer’s disease from other neurological disorders (eg: Parkinson’s disease, Huntington’s, cerebrovascular disease). At the least, changes in tau appear to be useful as sensors of the process of Alzheimer’s disease. Two phosphorylations, at serine 202 and at threonine 231 appear to occur very early in the course of the disease, prior to formation of filamentous inclusions or tangle formation, and prior to obvious signs of neuronal degeneration. It is tempting to speculate that these phosphorylations drive conformational changes in tau, but there is currently no clear evidence that this is the case. Conformational changes, recognized by the Alz50/MC1 antibodies, appear to occur as early as these two phosphorylations, prior to filament or tangle formation. It is possible that the increasing severity of these changes in tau cause cellular dysfunction and eventually neuronal death in Alzheimer’s disease. However, it is becoming increasingly clear that in at least some human tau mutation cases, and in some tau transgenic mice neuronal death may occur without the accumulation of abnormal tau. Neuronal dysfunction and death may thus occur by different mechanisms in Alzheimer’s disease and tau mutation cases. A better understanding of these mechanisms will be essential to the development of effective treatments for both types of disease. 51.03 Drug discovery approaches for the treatment of Alzheimer’s disease. Pangalos M N Wyeth Discovery Research, Prnceton, NJ, USA Discovering and developing novel therapeutics for diseases of the central nervous system is one of the most challenging, high cost and high-risk areas for the pharmaceutical industry. Neurodegenerative diseases are perhaps at the pinnacle of this challenge due in part to the incredible complexity of the central nervous system, and the relative lack of scientific understanding of key pathological processes. Many of the diseases in question remain devoid of effective drugs with no current therapies able to impact or modify disease pathophysiology. Thus the promise of therapies which can stop or reverse neurodegenerative processes in the brain are clear in terms of positive impact to patients, care givers as well as the socioeconomic state of healthcare systems. Present treatment standards for Alzheimer’s disease (AD) are primarily founded on the replenishment of the neurotransmitter acetylcholine and are poorly effective at best. I will present pre-clinical data for a number of drug discovery programs aimed at enhancing dysfunctional neurotransmitter systems in the degenerating brains of AD patients, in addition to data on a number of disease modifying approaches. The ultimate goal is to develop an array of complimentary and effective therapies for the treatment of AD. Page 74/101 - 10/05/2013 - 11:11:03
51.04 The use of MRI for tracking disease progression and assessment of novel therapies in Alzheimer’s disease Scahill R I Dementia Research Centre, Institute of Neurology, London, WC1N 3BG Brain atrophy is a macroscopic effect of the pathological hallmarks of Alzheimer’s disease (AD). Whilst definitive diagnosis of the disease requires neuropathological confirmation, brain atrophy can be visualised in vivo using MRI. Numerous studies have demonstrated whole brain and regional atrophy in individuals with AD compared with age-matched controls. However, due to the large inter-individual variation in brain size, there remains considerable overlap between the two groups, limiting the clinical utility of this technique in the earliest stages of the disease. Examining change over time within an individual has proved a powerful technique for separating individuals with AD from controls, as well as a means for tracking disease progression. Positional matching of serial scans allows quantification of brain atrophy1, a measure which has been used widely in the assessment of novel therapies. Using this technique individuals immunised with the AN1792 vaccine were shown to have greater rates of atrophy than placebo patients, raising the possibility that there may have been clearance of the amyloid plaques in those undergoing treatment2. Non-linear matching techniques e.g. fluid registration can give more specific information about atrophy location. Voxel-based statistical analysis of fluid parameters has proved useful in tracking disease progression from the presymptomatic stages through to established disease3. MRI is a powerful tool for revealing the natural history of AD as well as assessing the effect of potential therapies on this disease course. 52.01 Brain plasticity and antidepressant treatments: new cells, new connections Reid I Department of Mental Health, Institute of Medical Sciences, University Of Aberdeen, Foresterhill, Aberdeen AB25 2ZH The mechanisms that underpin brain plasticity are many and varied. The field has been a focus of research for decades now, and current conceptualisations have their roots in learning and memory research. Studies have turned more recently to psychiatric disease generally and to mood disorder in particular, with widespread interest in the reciprocal effects of stress and antidepressant treatments on neurogenesis. Attention has been drawn to the delayed onset of action of antidepressant activity and the argument advanced that this time-course mirrors the timing of antidepressant induced increases in neurogenesis rates. However, the delayed onset notion is increasingly challenged, and some antidepressant treatments, most notably electroconvulsive therapy, have clearly more rapid effects than others. More rapidly modified forms of plasticity than the production of new neurones may need to be considered in developing hypotheses about the aetiology of mood disorder. This presentation will focus on the role of changes in synaptic connectivity as it relates to the effects of stressors and antidepressant treatments. Links with neurotrophic hypotheses of the pathophysiology of mood disorder will be emphasised. 52.02 Genetic background influences neurogenesis and other associated phenotypes in the NK1-/- mouse McCutcheon J E, Morcuende S, Gadd C A, Lightman S L, Hunt S P Hippocampal neurogenesis has been implicated in the pathophysiology of depression due to the observation that most antidepressants will increase the number of proliferating cells. Indeed, neurogenesis may also be necessary for the therapeutic efficacy of antidepressant treatment. Current antidepressants exert their effects by targeting the neurotransmitter systems that are believed to regulate mood and emotion. Most commonly drugs which act on the serotonergic system are prescribed, however, the modulation of other monoamines, neuropeptides and glucocorticoids may also provide valid methods of treating these diseases. One of the most promising classes of compound to emerge recently have been the NK1 receptor antagonists. The NK1 receptor is the preferred receptor for the neuropeptide substance P and is found in many areas of the limbic system. Work using antagonists to this receptor and mice engineered to lack a functional receptor (NK1-/- mice) found antidepressant-like effects accompanied by increased neurogenesis, although this did not affect measures of learning and memory. Early clinical studies using NK1 receptor antagonists were generally positive, however, in later studies the drugs failed to produce any significant improvement above placebo. We have continued work using NK1-/- mice in our laboratory and have found that transferring the mutation onto different genetic backgrounds greatly influences the antidepressant-like phenotype, including the levels of neurogenesis. These differences may be related to genetically-conferred variation in HPA axis activity across individuals. This work may help to explain the failure of NK1 receptor antagonists, as well as many other drugs, to succeed in clinical trials. 52.03 Adult cytogenesis is susceptible to chronic stress Fuchs E, Czéh B Clinical Neurobiology Laboratory , German Primate Center, Göttingen, Germany As shown in various mammalian species, stress is among the most potent inhibitor of neurogenesis in the adult dentate gyrus. Parallel to these findings, numerous studies demonstrated that in chronic stress paradigms and various animal models of depression, the suppressed adult neurogenesis can be reversed by different types of antidepressant treatments including electroconvulsive stimulation. These findings resulted in much work on the concept that altered neurogenesis may contribute to the pathogenesis of depression and may play a significant role in, for example, the cognitive symptoms occurring in this disorder. In addition to neurogenesis, there is experimental evidence indicating that stress and antidepressant treatment can induce changes in gliogenesis (glial morphology and cell numbers). In a chronic social stress model in the tree shrew, we recently reported that in subordinate individuals, the number of GFAP-positive astrocytes was significantly reduced, but concomitant treatment with fluoxetine could block this effect. Furthermore, both stress and drug treatment altered the somal volume of the astrocytes. Besides their “housekeeping” functions, astrocytes are regarded as dynamic regulators of synaptic strength, synaptogenesis and neuronal production in the adult dentate gyrus. Astrocytes also possess receptors for neurotransmitters and steroid hormones that, similarly to receptors in neurons, can trigger electrical and biochemical events in the cell. Therefore, structural changes of astrocytes are likely to have an important functional significance for neuron–glia and neuron–neuron communication and are also of particular relevance for hippocampal volume changes observed in depressed patients. Page 75/101 - 10/05/2013 - 11:11:03
Page 1 and 2:
1.0 Paths to recovery: Modulating P
Page 3 and 4:
3.07 Congenital hypothyroidism alte
Page 5 and 6:
4.01 The effect of hippocampal slic
Page 7 and 8:
4.09 ß-adrenergic modulation of in
Page 9 and 10:
5.03 Constitutively active Ras and
Page 11 and 12:
6.07 Proteomic identification of bi
Page 13 and 14:
8.01 Dietary flavonoids stimulate P
Page 15 and 16:
9.04 Inducing neural differentiatio
Page 17 and 18:
10.02 The effect of PAT (thymulin r
Page 19 and 20:
10.10 Immuno-regulatory T cell func
Page 21 and 22:
11.04 Expression profile of mesench
Page 23 and 24: 12.01 Use of capillary chip based p
Page 25 and 26: 13.06 Contribution of synaptic cond
Page 27 and 28: 15.01 L-serine enhances the inhibit
Page 29 and 30: 16.03 Quantitative analysis of memb
Page 31 and 32: 18.03 Finding cells for replacement
Page 33 and 34: 20.01 Cannabinoid neuropharmacology
Page 35 and 36: 21.05 Spatial arrangement of cortic
Page 37 and 38: 23.04 Adenosine, astrogliosis and e
Page 39 and 40: 25.04 The L1 cell adhesion family a
Page 41 and 42: 28.05 The effects of the FAAH inhib
Page 43 and 44: 28.13 Genetic determinants of ethan
Page 45 and 46: 29.02 A HAP1-kinesin protein traffi
Page 47 and 48: 29.10 Identification of molecular d
Page 49 and 50: 29.18 Supporting study skills: work
Page 51 and 52: 33.02 Noradrenaline reuptake inhibi
Page 53 and 54: 35.01 Synchrony and sensory coding
Page 55 and 56: 37.01 Nitric oxide inhibition incre
Page 57 and 58: 37.09 Behavioural and electrophysio
Page 59 and 60: 39.06 The role of glutamate recepto
Page 61 and 62: 40.03 Live imaging of Per1 driven G
Page 63 and 64: 41.01 A polymorphism at the 3’ un
Page 65 and 66: 43.02 Neuroleptic treatment worsens
Page 67 and 68: 43.10 Biochemical estimates of SNAR
Page 69 and 70: 45.01 Mutant SOD1-PUMA knockout dou
Page 71 and 72: 47.03 VAP proteins Skehel P Center
Page 73: 49.04 Regulation of synaptic functi
Page 77 and 78: 53.04 The role of the pedunculopont
Page 79 and 80: 56.06 Dissecting exploratory behavi
Page 81 and 82: 57.01 Opioid Receptor Agonists’-
Page 83 and 84: 57.09 Cognitive rigidity and altere
Page 85 and 86: 57.17 An analysis of DJ-1 (PARK7) a
Page 87 and 88: 58.05 Differential effects of Inter
Page 89 and 90: 59.05 Blockade of paw incision-indu
Page 91 and 92: 60.07 2-Dimensional gel electrophor
Page 93 and 94: 63.02 Subpyrogenic systemic inflamm
Page 95 and 96: 64.08 Modulation of ketamine-induce
Page 97 and 98: 65.08 The anti-inflammatory role of
Page 99 and 100: 68.01 A comparison of carbachol and
Page 101: 69.06 Comparison of data analysis t
show all

Book of abstracts - British Neuroscience Association

Create successful ePaper yourself

Delete template?

Save as template?