About
Mental well-being is integral to population health and highly contributes to the functioning of individuals, families, communities and the social and economic prosperity of society. In fact, Psychiatric disorders have a huge impact not only in the individual but in society in general. Translational research in mental disorders - from bench to bedside – is crucial to give a step forward in the comprehension of such diseases. Thus, our main goal is to unravel the neurobiology behind Psychiatric disorders to ultimately contribute to improve patient´s lives, keeping in mind that an early intervention during development would improve patient´s outcome.
Our group is focus on neurodevelopmental disorders and their repercussions in the adulthood. We aim to explore some disorders such as ADHD, anxiety, depression and drugs abuse, with particular focus on psychostimulants. Additionally, the role of adverse life events and specific brain insults, such as traumatic brain injury, as triggers of Psychiatric disorders is also being investigated. Some specific questions have been raised by the team as follows:
1. Is there a link between early-life events and psychiatric events in the adulthood?
2. What are the consequences of drugs abuse?
3. Which is the neurobiology behind ADHD and the impact of pharmacological treatment?
4. How brain injury negatively impacts the blood-brain barrier leading to brain dysfunction?
At the cellular level, the team is mainly exploring neuroinflammatory and neurovascular alterations. Glial cells are considered the immune cells of the central nervous system playing a key role in physiological brain development, including in synaptogenesis. Study of association between brain health and immune changes is a main goal of our team. Moreover, glial cells play also an important role at the blood-brain barrier (BBB). This dynamic barrier highly selective, comprise by endothelial cells (ECs) that form brain capillaries, is responsible for the protection and maintenance of brain microenvironment proper for neural function. Notwithstanding, this unique brain immune quiescence can be altered in various pathological processes and it is now accepted that brain endothelial cells have an active role on brain function.
Pharmacologic and non-pharmacologic strategies, including physical exercise, will be pursued by the team in an attempt to improve or prevent neuropsychiatric alterations.
Main achievements
1. Methamphetamine induces a neuroinflammatory response, brain edema and BBB disruption, and parthenolide (present in feverfew plant) prevented these drug-induced effects.
2. Prenatal stress programs offspring peripheral metabolism in a sex-specific manner, emphasizing that the response to stress in critical periods of development may be sex-specific.
3. 2-Methylenedioxypyrovalerone, a synthetic cathinone, induces acute minor behavioral alterations without major classical neurotoxicity in a mice model.
Traumatic brain injury (TBI) leads to BBB disruption and a neuroinflammatory response, and NPY is able to revert the deleterious outcomes of TBI.
4. ADHD symptoms are highly prevalent among offenders and might have a modulating effect on the course of delinquent behavior as there is as association between ADHD symptoms and psychopathic traits.
5. The animal model of cuprizone (CPZ)-induced demyelination is interesting for studying the mechanisms involved in remyelination.
Publications
Scientific interests and ongoing research projects
1. Understanding the mechanisms by which psychiatric conditions, such as stress, ADHD and addiction, impact blood-brain barrier integrity and neuroinflammatory responses
2. Extracellular vesicles and physical exercise interplay in animal models of stress-related psychiatric disorders
3. Investigate the impact of maternal diabetes on offspring neurometabolism, neurodevelopment and behaviour, addressing sex-specific vulnerabilities and the specific role of gestation and lactation periods.
4. Pediatric multiple sclerosis (CHARGE; NEOS; OPERETTA2) and migraine (PROSPECT-2; REJOIN) clinical trials coordinate by Filipe Palavra.
5. Exploring the role of remyelination in early multiple sclerosis, using the cuprizone mouse model of the disease.
6. Study the molecular players and cellular routes used by immune peripheral cells to transmigrate into the brain.