Plasticity and regeneration of the nervous system and muscles

Plasticity and regeneration after injury in excitable tissues will be studied in the central nervous system, peripheral nerves and in skeletal muscles. Plasticity in the basal brain nuclei will be examined in several directions: A) animal models for neurodegenerative diseases (Parlinson’s and Huntington’s disease) will be used to investigate the role of interactions between different dopamine receptors, and the substance LEK-8829 will be tested as a possible antipsychotic drug. B) The importance of oxydative stress in neurodegenerative processes in the basal ganglia will be explored. C) Short-term and long-term molecular mechanisms involved in receptor sensitisation/desensitisation and their relationship to psychotropic drug abuse will be investigated. D) Mechanisms of induced plasticity and regeneration in the central nervous system will be investigated as well as ways how to modify these processes to contribute to functional recovery after brain injury. Different animal models and neurotransplantation will be used and the effects of experimental procedures will be analysed by behavioural testing, immunohistochemistry, receptor binding studies and molecular biology techniques. In the investigations of the peripheral nerve injury, possible triggering factors for collateral sprouting of axons will be explored. We will study sensory axon regeneration in the injured nerve in the absence of cell support in the nerve segment distally to the lesion site and possible effects of prior collateral sprouting or application of different trophic factors on such regeneration. In the studies of muscle plasticity, the effects of different stimulation patterns, denervation and paralyisis will be examined in more detail. In addition, the effects of thyroid hormones and muscle load on acetycholinesterase will be investigated. We will also try to develop a method for continuous chronic registration and analysis of bioelectric potentials (EMG, EEG) in freely moving experimental animals. Plasticity and regeneration are the most important processes responsible for functional recovery after injury to excitable tissues. Therefore, new knowledge in this field may on a long run contribute to improvement of therapeutic approaches in neurology and psychiatry.