Neuron-astrocyte signaling in depression: learning from astrocytes how to effectively treat depression

Depressive disorders affect more than 280 million people worldwide and its pathophysiology is still poorly understood. Depressive behavior is characterized in humans and animal models by persistent mood and cognitive impairments. These effects were consistently correlated with alterations in neuronal function and structure in cortico-limbic regions. While in physiological conditions astrocytes actively support neuronal function, our preliminary experiments show that modulating astrocytes causes resilience to the depressive pathology.

We hypothesize that the depressive pathology might result from over-activation of astrocytes in cortico-limbic networks. Thus, we propose to combine multidisciplinary approaches (behavioral, electrophysiological, transcriptomic) to IDENTIFY new region- and cell-specific molecular targets involved in depressive resilience. Moreover, we will produce novel tools to genetically manipulate these targets, and we will TEST their therapeutic potential.

Funding Agency

La Caixa Foundation

Project Reference

Project Members

Main Project Outcomes

S. Queirós, “Right ventricular segmentation in multi-view cardiac MRI using a unified U-net model”, in E. Puyol Antón et al. (eds) Statistical Atlases and Computational Models of the Heart. Multi-Disease, Multi-View, and Multi-Center Right Ventricular Segmentation in Cardiac MRI Challenge. STACOM 2021. Lecture Notes in Computer Science, vol 13131, pp. 287-295, Springer, Cham, 2022.

“Best Paper Award in the M&Ms-2 Challenge”, by M&Ms2 Challenge organizers and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society.

Main Project Outcomes

– Machado-Santos AR, Loureiro-Campos E, Patrício P, Araújo B, Alves ND, Mateus-Pinheiro A, Correia JS, Morais M, Bessa JM, Sousa N, Rodrigues AJ, Oliveira JF, Pinto L. 2022. Beyond New Neurons in the Adult Hippocampus: Imipramine Acts as a Pro-Astrogliogenic Factor and Rescues Cognitive Impairments Induced by Stress Exposure. Cells. 11:390.