NEURAL STEM CELL REGULATION IN BRAIN PLASTICITY
(@ NEUROSCIENCES AND PHARMACOLOGY)
We investigate modulators of neural stem cells to boost adult neurogenesis and oligodendrogenesis as a strategy for brain functional repair and aim to exploit them as a novel therapeutic platform to counteract brain pathologies such as Multiple Sclerosis, Epilepsy and Major Depressive Disorder.
To achieve this, the group employs a multidisciplinary approach, utilizing in vivo, ex vivo, and in vitro techniques to investigate the mechanisms underlying neural stem cell regulation. Our research encompasses areas like neuroplasticity, neuroinflammation, and the effects of physical exercise and cannabinoids on brain function. By exploring these avenues, we aim to develop novel interventions that can counteract brain pathologies and improve patient outcomes.
RESEARCH TEAM
Xapelli, Sara, PhD
GROUP LEADER
Sara Xapelli graduated in Biology from the Faculty of Sciences and Technology, University of Coimbra (2003) and obtained her PhD on the neuroprotective and antiepileptic role of neuropeptide Y at the Center for Neuroscience and Cell Biology (CNC), University of Coimbra (Portugal), the University of Southern Denmark, and the University of Alberta (Canada) (2008). She conducted her first postdoc at CNC, with an internship at the University of Southern Denmark, and a second postdoc at Instituto de Medicina Molecular João Lobo Antunes (iMM) where she pioneered research on neural stem cells. Since 2018, Sara Xapelli is an Assistant Professor and a PI at FMUL. She is vice-president of the Portuguese Society for Neuroscience, member of the Mind-Brain College Executive Committee, and member of the General Meeting Board of the Portuguese Society of Stem Cells. Sara has received numerous awards, including the ISN Career Development Grant (2021) and the IBRO Early Career Award (2022).
ORCID ID:0000-0001-6854-2509
E-mail: sxapelli@medicina.ulisboa.pt
Erkizia-Santamaria, Inês, PhD
Postdoc Researcher
Ines graduated in Pharmacy (University of the Basque Country UPV/EHU, 2019), and completed her PhD on the mechanism of action and antidepressant effects of psilocybin (2024). Her research focuses on finding the neurobiological mechanisms involved in psychiatric illnesses, in particular, mood disorders, with the long-term goal to find new pharmacological tools to ameliorate their treatment. As such, she employs in vivo (animal models of psychiatric disorders, behavioural assessments, brain microdialysis, neuroimaging), ex vivo (electrophysiology) and in vitro techniques.
ORCID: 0000-0002-6163-4571
E-mail: iesantamaria@medicina.ulisboa.pt
Ribeiro-Rodrigues, Leonor, PhD
Postdoc Researcher
Leonor is a Biologist (BSc, Universidade de Lisboa) and Neuroscientist (MSc and PhD, Universidade de Lisboa) specialized in epilepsy. Her PhD project focused on the relation between epilepsy, neurogenesis, cognition and BDNF/TrkB-FL signaling pathway. To investigate this, she induces an in vivo model of epilepsy and performs distinct techniques, such as behavioral tests, immunohisto-chemistry, western blotting and in vivo surgeries.
ORCID: 0000-0001-7788-8210
E-mail: leonorrodrigues@medicina.ulisboa.pt
Paulo, Sara, PhD
Grants officer
Sara is a Biochemist (BSc, University of Aveiro) and a Neuroscientist (MSc and PhD, Lisbon Medical School, Universidade de Lisboa). Her PhD focused on the impact of Aβ, obesity and physical exercise on hippocampal and hypothalamic neuroplasticity, in the context of Alzheimer’s disease-related pathology. Sara is experienced in techniques such as rodent behaviour, immunofluorescence, microscopy, cell culture and ELISA.
Currently, she is supporting research as pre-award grants officer for the EU-funded PANERIS project.
ORCID: 0000-0001-7668-2173
E-mail: sara.paulo@medicina.ulisboa.pt
Mateus, Joana, MSc
PhD Student (GIMM PhD Studentship)
Joana is a Biochemist (BSc in Biochemistry, Universidade de Lisboa) and Neurobiologist (MSc in Cellular and Molecular Biology, Universidade de Coimbra) working on adult oligodendrogenesis. She investigates how physical exercise and modulation of BDNF, cannabinoid, and adenosine A2A receptors enhance oligodendrocyte formation from SVZ neural stem cells. For this, she uses in vitro (SVZ-neurosphere cultures) and in vivo techniques (Cuprizone mouse model, behavior analysis) coupled to cellular and molecular assays. In parallel, she works as a project manager for the EU-funded PANERIS project.
ORCID: 0000-0003-1606-292X
E-mail: joana.mateus@medicina.ulisboa.pt
Moreira, João, MSc
PhD Student
João is a Neurobiologist (BSc in Biomedical Sciences, Universidade do Algarve; MSc in Cellular and Molecular Biology, Universidade de Coimbra) working on postnatal and adult neurogenesis. Currently, he is interested in understanding the effects of caffeine on adult neurogenesis and synaptogenesis. To accomplish this, João uses both in vitro approaches, namely the neurosphere culture and immunocytochemistry, as well as, in vivo techniques, such as behavior analysis and immunohistochemistry.
ORCID: 0000-0002-7736-844X
E-mail: joaomoreira@medicina.ulisboa.pt
Rosário Leandro, Madalena, BSc
MSc Student
Madalena is a Biologist currently completing her MSc in Neuroscience at the Faculdade de Medicina, Universidade de Lisboa. Her work focuses on neurogenesis in the context of epilepsy, with an emphasis on the BDNF/TrkB-FL signaling pathway. Using a rat model of mesial temporal lobe epilepsy, she applies techniques such as immunohistochemistry.
ORCID: 0009-0005-5172-7693
E-mail: madalena.leandro@medicina.ulisoa.pt
Pedro, Esteves, BSc
MSc Student
Pedro is a Biochemist (Bsc in Biochemistry, Universidade de Évora), and a Master’s student in Biopharmaceutical Sciences at the Faculty of Pharmacy, Universidade de Lisboa. He is currently developing his thesis project with the group at the Faculty of Medicine, Universidade de Lisboa, on the role of adult hippocampal neurogenesis and the effects of physical exercise and endocannabinoid signaling in mouse models of depressive-like behavior.
ORCID: 0009-0005-9555-1618
E-mail: pedro-esteves@edu.ulisboa.pt
INTERNATIONAL COLLABORATORS
Carlos Fitzsimons, University of Amsterdam, Swammerdam Institute for Life Sciences Netherlands, Amsterdam, The Netherlands
Daiva Baltriukienė, Vilnius University, Lithuania.
Jorge Valero, Instituto de Investigación Biomédica de Salamanca, Spain
Katarzyna Starowicz, Institute of Pharmacology, Polish Academy of Sciences, Poland
Klaudia Lustyk and Karolina Pytka, Jagiellonian University Medical College, Poland
Neil Dawson, Lancaster University, UK
Sabine Lévi, ESCPI, Paris, France
RECENT PROJECTS
International:
2024 – 2026: Pan-European Network for Neuroscience Research Infrastructure and Strengthening of Support capacities. Funded by: European Commission (HORIZON-WIDERA-2023-ACCESS-04-01) (Project number: 101160180). – Working Group Leader
2023 – 2026: Collaborative learning and innovative teaching for brain drug screening. Funded by: European Commission (Cooperation partnerships in higher education (KA220-HED). (Project number: KA220-HED-6324368A). – PI
2023 – 2026: Microglial modulation of environmental stimulation effects on adult neurogenesis. Funded by: Spanish government (Project number: PID2022-140525NB-I00) – Collaborator
National:
August 2025 – July 2028: Targeting neural stem cells for major depressive disorder: studying the synergy between cannabinoid type 2 receptors and physical exercise (STEM-CARE). Funded by: FCT. – PI
SELECTED PUBLICATIONS
Lourenço, D. M., Zavalko, S., Duarte, A. L., Sá-Santos, S., Mateus, J. M., Rodrigues, R. S., Miranda-Lourenço, C., Mouro, F. M., Viais, R., Sebastião, A. M., Solá, S., Diógenes, M. J., & Xapelli, S. (2025). Cannabidivarin mitigates motor and cognitive impairments in a female mouse model of Rett syndrome. Life sciences, 378, 123846. https://doi.org/10.1016/j.lfs.2025.123846
Rodrigues, R. S., Moreira, J. B., Dias, P., Sebastião, A. M., & Xapelli, S. (2025). The Effects of Exercise-Associated Factors on Hippocampal Progenitor Cell Dynamics Are Mediated by Cannabinoid Type 2 Receptors. Journal of neurochemistry, 169(5), e70091. https://doi.org/10.1111/jnc.70091
Ribeiro-Rodrigues, L., Fonseca-Gomes, J., Paulo, S. L., Viais, R., Ribeiro, F. F., Miranda-Lourenço, C., Mouro, F. M., Belo, R. F., Ferreira, C. B., Tanqueiro, S. R., Ferreira-Manso, M., Umemori, J., Castrén, E., Paiva, V. H., Sebastião, A. M., Aronica, E., Campos, A. R., Bentes, C., Xapelli, S., & Diógenes, M. J. (2025). Cleavage of the TrkB-FL receptor during epileptogenesis: insights from a kainic acid-induced model of epilepsy and human samples. Pharmacological research, 215, 107707. https://doi.org/10.1016/j.phrs.2025.107707
Soares, R., Lourenço, D. M., Mota, I. F., Sebastião, A. M., Xapelli, S., & Morais, V. A. (2024). Lineage-specific changes in mitochondrial properties during neural stem cell differentiation. Life science alliance, 7(7), e202302473. https://doi.org/10.26508/lsa.202302473
Rodrigues, R. S., Moreira, J. B., Mateus, J. M., Barateiro, A., Paulo, S. L., Vaz, S. H., Lourenço, D. M., Ribeiro, F. F., Soares, R., Loureiro-Campos, E., Bielefeld, P., Sebastião, A. M., Fernandes, A., Pinto, L., Fitzsimons, C. P., & Xapelli, S. (2024). Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress. Translational psychiatry, 14(1), 170. https://doi.org/10.1038/s41398-024-02877-0
Lourenço, D. M., Soares, R., Sá-Santos, S., Mateus, J. M., Rodrigues, R. S., Moreira, J. B., Vaz, S. H., Sebastião, A. M., Solá, S., & Xapelli, S. (2023). Unravelling a novel role for cannabidivarin in the modulation of subventricular zone postnatal neurogenesis. European journal of pharmacology, 959, 176079. https://doi.org/10.1016/j.ejphar.2023.17607
Paulo, S. L., Miranda-Lourenço, C., Belo, R. F., Rodrigues, R. S., Fonseca-Gomes, J., Tanqueiro, S. R., Geraldes, V., Rocha, I., Sebastião, A. M., Xapelli, S., & Diógenes, M. J. (2021). High Caloric Diet Induces Memory Impairment and Disrupts Synaptic Plasticity in Aged Rats. Current issues in molecular biology, 43(3), 2305–2319. https://doi.org/10.3390/cimb43030162
Paulo, S. L., Ribeiro-Rodrigues, L., Rodrigues, R. S., Mateus, J. M., Fonseca-Gomes, J., Soares, R., Diógenes, M. J., Solá, S., Sebastião, A. M., Ribeiro, F. F., & Xapelli, S. (2021). Sustained Hippocampal Neural Plasticity Questions the Reproducibility of an Amyloid-β-Induced Alzheimer’s Disease Model. Journal of Alzheimer’s disease : JAD, 82(3), 1183–1202. https://doi.org/10.3233/JAD-201567
Ribeiro, F. F., Ferreira, F., Rodrigues, R. S., Soares, R., Pedro, D. M., Duarte-Samartinho, M., Aroeira, R. I., Ferreiro, E., Valero, J., Solá, S., Mira, H., Sebastião, A. M., & Xapelli, S. (2021). Regulation of hippocampal postnatal and adult neurogenesis by adenosine A2A receptor: Interaction with brain-derived neurotrophic factor. Stem cells (Dayton, Ohio), 39(10), 1362–1381. https://doi.org/10.1002/stem.3421