The production of new astrocytes in the adult human brain may contribute to an improvement in depressive and anxious behavior in patients with neuropsychiatric diseases, as well as to the restitution of neural cells in the hippocampus, a brain region important for the control of emotional and cognitive behaviors. These are the main conclusions of a study carried out by a research team from the ICVS, and recently published in the journal Molecular Psychiatry.
Throughout adulthood, the human brain retains the ability to generate new neurons (neurogenesis) and new astrocytes (gliogenesis) in a specific region – the hippocampus. These new cells derive from the same population of progenitor cells and contribute to the formation of new memories, emotions and learning. However, the study of the generation of new astrocytes (gliogenesis) has been neglected, particularly with regard to their contribution to the normal function of the hippocampus. Furthermore, finding appropriate experimental approaches to discover the role of gliogenesis in the adult brain has proven to be a major challenge, given the lack of tools that allow dissociating the specific contribution of this process (gliogenesis) in isolation from the formation of new neurons (neurogenesis). This has prevented the possibility of drawing valid conclusions about the individual participation of each type of newborn cell in the development and evolution of a disease (pathogenesis), as well as in the treatment of neuropsychiatric disorders.
Luísa Pinto, Joana Martins-Macedo and Eduardo D. Gomes (from left to right)
In order to find new conclusions about this process, ICVS researchers Luísa Pinto, Joana Martins-Macedo and Eduardo D. Gomes focused on studying and establishing a link between gliogenesis and depression.
After using a transgenic animal model to selectively eliminate the generation of new cells in the adult hippocampus and assess its impact on different behavioral domains, Luísa Pinto stated that it was possible to observe “a different role for immature and mature cells in the adult brain, with regard to the manifestation of emotional and cognitive deficiencies. Considering the potential of this animal model to transiently but effectively eliminate all newly born progenitor cells in the hippocampus (affecting both neurogenesis and gliogenesis), we thought about introducing progenitor cells restricted to the glial lineage (incapable of generating new neurons), from an external source, into the adult hippocampus. This approach would allow us to understand the specific role of newborn glial cells/astrocytes (from external sources), in a time window when the natural processes of neurogenesis and gliogenesis in adult animals are not occurring endogenously”.
Joana Macedo describes that in this context, and using the tools previously described, “we were able to be the first group to demonstrate the specific contribution of glial progenitor cells (mostly new astrocytes), not only to normalize gliogenesis, but also to restore the normal levels of adult neurogenesis that usually occur in the hippocampus of these animals. Most importantly, we demonstrated the importance of gliogenesis in the recovery of anxious and depressive behaviors”. This work adds to our knowledge of the role of gliogenesis, as it revealed that the “production of new astrocytes effectively contributes to an improvement in depressive and anxious behavior”.
As Eduardo D. Gomes explains, the future involves finding “new ways” to treat various neuropsychiatric and neurodegenerative conditions, through new drugs that modulate brain gliogenesis or, more importantly, through personalizing patient treatment.
This study was developed in collaboration with another ICVS research team, led by Dr. António Salgado and, in particular, with great involvement from Dr. Angelo Lepore, from Thomas Jefferson University, in the USA, and also in synergy with the Center for Neuroscience and Cell Biology of Coimbra.
