Seite - (000190) - in Biomedical Chemistry: Current Trends and Developments

(heteroreceptors). The activity of GABAergic synapses is important in the regulation of the overall activity of neuronal networks, refraining the effect of excitatory activity. In the cerebral cortex there are two main classes of neurons, pyramidal cells and interneurons, which use glutamate and GABA as main neurotransmitters, respectively. Interneurons comprise 20–30% of the 15 cortical neuronal population and are locally projecting cells that control and synchronize the output of pyramidal neurons. Increasing evidence suggests that disruption of the excitatory-inhibitory (E/I) balance maintained by pyramidal cells and interneurons is linked to the etiology of multiple neuropsychiatric and ischemic conditions (Obrenovitch, 2008; Wang, 2011). Research in cerebral ischemia and excitotoxic neuronal damage has been mainly focused on the excitatory mediators and much less attention was given to the changes in GABAergic activity (Schwartz- Bloom, 2001). The release of GABA in the ischemic brain and the consequent activation of GABAA receptors may be neuroprotective through reduction of membrane depolarization. Although Cl- entry through GABAA receptors in association with overactivation of glutamate receptors may further increase the influx of water and cell swelling, strategies to increase GABAergic neurotransmission, targeting both sides of the synapse, have been quite efficient in models of ischemia (Schwartz-Bloom, 2001). The impairment of GABAergic synaptic transmission in brain ischemia is partly due to a down- regulation of synaptic GABAA receptors, which may contribute to the ongoing neuronal excitability and possibly to neuronal death (Schwartz- Bloom, 2001). Furthermore, exposure of hippocampal slices to oxygen- and glucose-deprivation was shown to induce an early release of GABA by exocytosis, followed by a delayed phase of neurotransmitter release mediated by reversal of the plasma membrane transporter (Allen, 2004). The balance between excitation and inhibition is an important mechanism in epilepsy, with inhibitory GABAergic regulation considered the main disorder in epilepsy (Schindler, 2008). Evidence shows that during the onset of the status epilepticus endocytosis of GABAA receptors takes place in the hippocampus, decreasing post-