Neuromodulation of astrocytes as a regulator of inflammation in the Central Nervous System.

Although having different etiologies chronic pain [1, neurodegenerative diseases such as Parkinson¿s [2-5, and psychiatric disorders [6, share some common molecular and biochemical processes [7. For example, it has been shown that inflammation plays an important role in the physiopathology of these diseases [8-10. Astrocytes, the most abundant cell in the CNS, modulate synaptic activity and provide metabolic and trophic support to neurons [11. It has been shown that during chronic pain, epilepsy, and neurodegenerative diseases astrocytes produce a set of molecules that can be beneficial or detrimental to neurons. For instance, the increases in asynchronic neuronal discharges, such as those achieved during status epilepticus lead to an increase in the expression and release of pro-inflammatory molecules, reactive oxygen species (ROS), and pro-apoptotic molecules [12-14. Release of these molecules can induce neuronal dysfunction and death. Importantly, these results suggest that electrical activity can directly modulate signaling pathways that impact astrocyte gene expression. Recently, electrical neuromodulation (ENM) has been shown to give positive and long-term results in Parkinson¿s, dystonia, essential tremor, and chronic pain [15-17. However, the mechanisms of action behind the beneficial effects of ENM are poorly understood. Recent studies have suggested that ENM can work by resetting the neuron¿s electrical properties, which induces changes in the oscillatory circuits involved in disease genesis [18. However, less is known about how EMN can affect other cells in the CNS. For example, there is no data showing if ENM may work by regulating astrocytes activation and production of inflammatory, oxidative and/or apoptotic molecules. Additionally, it is unknown whether ENM can modulate the production of these molecules depending on the frequency of stimulation and type of electrical stimuli. Therefore, the goal of the present project is to evaluate ENM capability of regulating the astrocyte physiology and the impact of this regulation in the function and survival of neurons under an inflammatory-induced environment.