The Neuroscience and Disease research area brings together researchers with the shared goal of unravelling the root causes of neurodegenerative and neuropsychiatric disorders. Using integrative approaches spanning molecular, cellular, circuit and behavioral neuroscience and brain imaging, we aim to define an hierarchy of events shifting normality into disorder. Through the exploration of different potential candidates, such as altered synaptic neuromodulation, mitochondrial dysfunction, neurovascular coupling and neuroinflammation, our long-term goal is to develop novel interventions and discover biomarkers for brain and vision disorders. In this endeavor, our research is supported by a unique and strong interface with the Coimbra University Hospital (CHUC).
The work of this thematic line on the function of the nervous system addresses fundamental questions related to biological processes such as learning and memory formation and social behavior. We use recent advances in genetic, viral, and optogenetic approaches, together with ex-vivo and in vivo electrophysiology, in-house developed novel micro(bio)sensors for in vivo measurements, and imaging and behavior analyses to identify neuronal pathways, functional networks and circuits controlling specific behaviors implicated in neuropsychiatric disorders.
Another major contribution of this thematic line is to advances in understanding the molecular and cellular basis of neurodegenerative diseases such as Alzheimer’s (AD) and Huntington’s (HD) disease, as well as vision disorders. Our studies implicate mitochondrial dysfunction, redox changes and cerebrovascular impairments in these disorders, and identified the adenosine A2A receptor as an important target for therapy in AD and retinal degeneration. These preclinical studies are complemented by translational and clinical research, aiming to identify human biological markers that reflect the onset of pathology in neurodegenerative disorders. The study of age-related neurodegeneration is paralleled by the investigation of aging as a risk factor for chronic diseases, and of strategies to rescue neurovascular coupling and hypothalamus functionality to delay the aging phenotype.
Our strategic goal is to address a major medical and societal challenge of the twenty first century: how genetics, life events and aging initiate brain and vision disorders, and through this knowledge understand how these diseases can be early diagnosed, staged, and treated.