Understanding the Role of Dopamine in Astrocyte Mediated Brain Signaling and Function

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Dopamine is one of the major neurotransmitters in the central nervous system and plays a central role in the dopamine reward pathway. Many drugs of abuse interact with dopamine neurons present in the midbrain leading to the release of dopamine via the mesocorticolimbic pathway. Additionally, alterations in dopamine level are connected to various neurological conditions such as Parkinson's disease, Schizophrenia, and Alzheimer's. While elevated dopamine levels have been shown to induce morphological changes in astrocytes in culture, the role of dopamine-activated astrocytes in neuroinflammation is not clearly understood. Astrocytes act as mediator cells in the brain. During pathological conditions, both microglia and astrocytes are activated, but astrocytes communicate with neurons and play a crucial role both in protection and destruction of neurons. We performed a series of studies showing time-dependent modifications of astrocytic processes resulting from dopamine exposure. We tracked changes in fine astrocytic process using atomic force microscopy and found dopamine-induced remodeling in fine astrocytic processes. We also observed concentration-dependent overexpression of GFAP and of IL6 cytokine release in dopamine treated astrocytes. However, we did not find detectable levels of the proinflammatory cytokine TNFα production even at high concentrations of dopamine. We also discovered that dopamine treated astrocytes are more cytotoxic to neurons from our experiments of treating astrocyte conditioned media in neuroblastoma N2a cells.