Volume 1

The revision of the EU Directive on the protection of animals used for scientific purposes / House of Lords. European Union Committee.

  • Great Britain. Parliament. House of Lords. European Union Committee
Date:
2009
Catalogue details

Licence: Open Government Licence

Credit: The revision of the EU Directive on the protection of animals used for scientific purposes / House of Lords. European Union Committee. Source: Wellcome Collection.

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    A3. Human neurochemistry and therapeutics: Combining non-invasive techniques to study the effect of drugs on the human brain as an alternative to animal experiments This research project is currently being funded by the Dr Hadwen Trust and conducted by Dr G Barnes, Dr A Hillebrand, Dr P Furlong and Dr S Hall at Aston University. The main focus is the development and application of non-invasive functional imaging techniques in the study of cortical structure and function. The work encompasses fundamental neuroscience and clinical research aimed at understanding and improving treatment of a range of neurological illnesses which are very often studied in primates. Many mental conditions, such as depression, are difficult to characterise in other species. Despite this, many animals including primates continue to be used in research into human mental illness. To understand and ultimately combat diseases such as schizophrenia, dementia, depression and developmental disorders such as autism, we need to study human beings. There is now a range of functional neuroimaging techniques that allows non-invasive measurements from the intact human brain. The long-term goal of this project is to provide models of human neurochemistry linked to the electrical behaviour in the cerebral cortex. The ability to directly and accurately measure the electrical profile of drug- induced change in the human brain would have a wide spectrum of applications, relating to the understanding of normal brain function, treatment of neurological disorders and the targeted design of new drugs. The Aston research is investigating the use of two non-invasive imaging techniques: magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS). Combining these two techniques permits more detailed information to be collected than is possible with either method singly. MEG uses highly sensitive magnetic field sensors to determine neuronal electrical activity on a millisecond by millisecond basis. It provides high spatial and temporal resolution images of the electrical behaviour of the cortex, but no chemical or anatomical information. The Aston group has demonstrated that non-invasive MEG studies can effectively replace certain invasive experiments on primates [1]. MRS uses high-strength magnetic fields to determine the chemical composition of regions of the brain, based on the resonant frequency of particular atoms, such as hydrogen. It can show the distribution of targeted neurotransmitters and various metabolites across the brain [2]. MEG has proved to be extremely successful at identifying the cortical areas affected by the modulation of GABA receptors and at monitoring changes in activity over time following the administration of diazepam, used as a pharmacological tool. Comparative data were collected with targeted pharmacological MRS during diazepam uptake, to provide anatomically relevant chemical measures. This combination of MEG and MRS into a pharmaco-imaging method is a novel approach [3] that possesses great potential for drug development and the replacement of primate experiments. Work is continuing to further develop and optimise this pharmaco-imaging method, and to investigate painkillers and the drug zolpidem used in the treatment of brain injury. REFERENCES 1. Hall S D, Holliday I E, Hillebrand A et al (2005) The Missing Link: analogous human and primate cortical gamma oscillations. Neuroimage 26:13-17. 2. Ugurbil K, Adriany G, Andersen P et al (2000) Magnetic resonance studies of brain function and neurochemisty. Ann Rev Biomed Eng 2:633-660. 3. Hall SD & Adjamian P (2006) The Chemistry of Cognition. In: Gazzaniga M S, Senior C & Russel T (eds), Methods in Mind. Cambridge USA: MIT Press. A4. Multiple sclerosis: Functional analysis of the T-cell immune response in multiple sclerosis by gene silencing Professor Daniel Altmann at Imperial College London has a research grant from the Dr Hadwen Trust for a pilot study to apply gene silencing techniques to human cell lines established from multiple sclerosis patients. The aim is to characterise key changes in the control of immune function in vitro with the longer term goal of developing an in vitro model system for studying key candidate immune system genes. There have been more than 10,000 publications on the induction of an animal surrogate for multiple sclerosis, called experimental allergic encephalomyelitis, in rodents, rabbits and monkeys, including macaque monkeys (1, 2]. Animals suffer inflammation and damage to the nervous system that may result in paralysis, in experiments that can cause distress and suffering. Pre-clinical primate experiments are largely confined to the Netherlands and the USA [3].