Page - (000194) - in Biomedical Chemistry: Current Trends and Developments

circuitries, modulating signaling in many pathways. While recent studies show that some of this processes seems to be age-related and, therefore, transitory in nature (Sun, 2013), others were shown to directly modulate learning and behavior. Astrocyte signaling and gliotransmission were proposed to represent a highly evolved integrative interface in brain communication, coupling slow modulatory signaling from different sources with fast synaptic transmission, contributing to fine tuning the synaptic circuitry according to the environmental surroundings (Araque, 2014). Microglia, rather than just reacting to injury or infection, were shown to prune synapses by monitoring synaptic transmission (Schafer, 2013), refining neuronal circuitry and improving plasticity (Salter, 2014). In the hippocampus (and other brain regions), microglia is required for proper function of the glutamatergic synapses. Several studies have shown that local microglia-derived BDNF is essential for long term potentiation and depression, which represents a critical mechanism for memory and learning (Salter, 2014). In accordance, with increasing data revealing the role of microglia in many neuronal disorders, such as AD, PD, mood disorders, neurophatic pain or addictive behavior. Knowledge gained in this field is expected to contribute to the design of new therapeutic approaches in most of such conditions. 2.4.5 Cognitive Enhancement Currently, a number of pharmacologic approaches traditionally used to treat medical conditions are used as cognitive enhancers. Medications for ADHD and narcolepsy targeting the monoaminergic systems, such as methylphenidate and modafinil, were found to provide acute enhancing effects to healthy individuals (Repantis, 2010). Other compounds, like donepezil, rivastigmine or galantamine are drugs that improve cognition targeting the cholinergic system. As discussed for dopamine, the effect of cholinergic enhancers is usually represented by a bell shaped curve, meaning that excessive doses may reduce the cognitive performance (Balsters, 2011). The long-term consequences of such drugs remain mostly unexplored and its regulation is yet to be addressed by policymakers and other stakeholders. Their use is particularly