Serotonin (5HT)1A receptor and its second messenger pathways, and the neuroprotective potential of specific 5-HT1A receptor agonists
01 / 2000 - 01 / 2004
5HT (serotonin) is widely distributed in the brain. A large number of brain structures is innervated by serotonergic neurons. Most of the serotonergic innervation originates from the raphe nuclei in the midbrain. The action of serotonin is mediated through a large number of receptors, which can be excitatory or inhibitory. This difference in receptor properties and the large distribution of the serotonergic system throughout the brain makes serotonin an excellent candidate for neuromodulation. The 5HT1A receptor belongs to the family of inhibitory G-protein coupled receptors. This receptor is found on the soma of serotonergic neurons in the raphe nuclei (autoreceptors), and on neurons that are innervated by the serotonergic system (postsynaptic receptors). Activation of the 5HT1A receptor triggers a number of cellular processes, which directly influence the properties of a neuron. This project will focus on the 5-HT1A mediated cellular changes and underlying second messenger systems. The effects of acute and chronic 5-HT1A receptor stimulation will be investigated both in vivo and in vitro models. Because of its inhibitory effect on neurons part of the work will exist of examining the neuroprotective potential of specific 5-HT1A receptor agonists against excitotoxicity, a form of neurotoxicity found in a number of neurodegenerative diseases like stroke or Alzheimer's disease.