Astrocyte dopamine D1 receptor signaling in depression

Major depressive disorders (MDD) represent a global challenge. Although many recent initiatives have resulted in new antipsychotic drugs, their efficacy is not optimal.

One possible reason for this is that the prevailing paradigm for drug development is based on the neuron-centric view of how the central nervous system (CNS) copes with diseases.

In the fellowship, I will study neuroglia, the nonneuronal cells responsible mainly for maintaining homeostasis in the CNS.

Failure in the function of these cells can set the course for neurological conditions, including psychiatric diseases and MDD. Thus, targeting neuroglia has recently been viewed as a new translational ground for drug development. The present proposal is therefore based on our understanding of the potential role of neuroglia in brain disease.

One of the major neurotransmitters, dopamine, is known to play an important role in MDD. I will examine the regulation of astrocytes, a major type of neuroglia, by dopamine.

Based on the state of the art, I hypothesise that astrocytic dopamine D1 receptor signalling may be involved in the pathophysiology of MDD.

Through innovative methodological approaches I will study the regulation of astrocytic D1 receptor signalling at the cellular level in an experimental model of MDD. Moreover, this project will explore D1 signalling in vivo to validate the results obtained on isolated cells.

The proposed research will provide a new framework that includes astrocytes and the mechanisms underlying the dopaminergic modulation in depression. This will afford novel cellular targets for treatment of MDD associated with dopamine D1 receptor signalling.

In addition, a comprehensive two-way transfer of knowledge is envisioned to bring together competences and experiences necessary for the proposed research. The fellowship will facilitate my career development and enable me to get established in the field.