Seite - (000191) - in Biomedical Chemistry: Current Trends and Developments

synaptic inhibitory currents (Naylor, 2005a; 2005b). Glutamate and GABA transporters also affect the excitatory/inhibitory balance. Glutamate transporter activity could trigger GAT reversal activity in astrocytes, by elevating intracellular Na+ levels. This glutamate/GABA exchange may act as a negative feedback to decrease excitation during seizures (Gadea, 2001; Heja, 2012; Wu, 2014). Neuronal network remodeling is also common in epilepsy, including loss of GABAergic interneurons and axon growth. The formation of new excitatory circuits may increase seizure intensity (Wu, 2014). Excitatory/inhibitory balance determination shows that inhibition superimposes on pyramidal neurons during initiation of seizure events, shifts towards excitation during seizures propagation, and eventually inhibition dominates again during seizures termination (Murase, 2014). The mechanism underlying such homeostatic changes involves increased glutamate signaling and alterations in GABAergic transmission, related to suppressed presynaptic inhibition and GABAergic vesicular depletion (Trevelyan, 2013). Several evidences show that GABA plays an important role in the cognitive features of schizophrenia (Gonzalez-Burgos, 2011). Most domains of GABAergic signaling are altered in schizophrenic patients, such as in the expression of GAD 65 and 67, and GAT1 (Pierri, 1999; Hashimoto, 2008). Alterations in GABAA receptors were also described in schizophrenic patients (Fatemi, 2013), depending on the targeted brain region, GABAergic transmission can be either increased or decreased (Deidda, 2014). The imbalance of excitatory/inhibitory stimulus has also been linked to schizophrenia-related GABAergic dysfunction (Lewis, 2005). Hypofunction of NMDARs and increased D2 activity leads to hypostimulation of GABAergic neurons (Lewis, 2005). GABAergic excitatory/inhibitory imbalance and consequent discoordination between GABAergic and glutamatergic firing are critical to the cortical abnormal function and consequent cognitive deficits reported in schizophrenia (Sullivan, 2012). In AD, dysfunction of the GABAergic system may also play a role in the cognitive impairment associated with this disease. It has been shown that AD patients display lower GABA levels in the brain and in cerebrospinal fluid (CSF) (Grouselle, 1998). Although the AD