Research Activities

1. Autism spectrum

2. Natural drugs and neuroprotection

3. Peripheral receptors and neuroimmunomodulation

1 - Autism spectrum

Autism is a neural development-related disorder characterized by impairment of social interaction, behaviour and communication skills. However, biological causes and biochemical mechanisms involved in such disease still remain unsolved. Some important aspects this project intends to emphasize is the dynamical interaction between clinicians and researchers within the whole biomedical field, to create an open environment for the discussion of different hypothesis and finally, to improve the existing training programme for professionals in the area of study. We do think that all this together would help the current development of novel therapeutics strategies to treat the disease.

Aims:

• To better understand the etiology of autism by obtaining solid results that would generate new options for drug therapy;
• To identify peripheral markers for clinical diagnosis of autism;
• To evaluate the expression of receptors for endogeneous immunomodulators (glutamate, serotonine, dopamine, acethylcholine) in leukocytes of patients with autism and their mothers;
• To test the possible effects of neuroimmunomodulators in leukocyte primary cultures isolated from autistic patients and their mothers;
• To study the potential effects of antipsychotic agents in autism;
• Characterization and quantification of microRNA in leukocytes from autistic patients;
• To study both neural and peripheral dysfunctions in an in vivo model of autism (Wistar rats).

Projects:

• Valproic acid-induced in vivo model of autism in Wistar rats: characterization and quantification of behavioural, morphological and biochemical parameters;
• Regulation of glial functions upon exposure to atypical antipsychotic risperidone;
• Risperidone-induced effects over astroglial morphology and S100B secretion;
• The effects of antipsychotic agents in primary cultures of astrocytes and neurons;
• Screening and validation of different neuroimmunomodulators in autistic patients.

2 - Natural drugs and neuroprotection

During the last two decades, several studies were performed in order to elucidate the putative biological properties of natural compounds. As a matter of fact, many of them have remarkably shown therapeutic potential. Resveratrol as well as green tea-derived polyphenoles are a couple of good examples, demonstrating promising effects against aging and neurodegenerative diseases. Our lab has previously reported that both resveratrol and epicatechin gallate are able to significantly increase glutamate uptake and the secretion of S100B trophic factor in astrocytes. Moreover, we showed that both compounds are able to exert either genoprotective or genotoxic effects in a time and dose-dependent manner, meaning that small doses of such polyphenoles included in our daily diet may trigger a beneficial genoprotective function and therefore, they could become an excellent therapeutic tool in neurological diseases associated to oxidative stress scenarios. On the contrary, the observed high dose-related antagonic effects highlighted the importance of a control and balanced supplementation of our diet with exogenous antioxidants.

Aim:

• To screen the potential neuroprotective effects of several natural compounds in a variety of models for neural injury.  

Models:

Neuronal and glial primary cultures; animal models of human disease (Parkinson disease and stress).

Projects:

• Therapeutic potential of resveratrol against hydrogen peroxide-induced in vitro and in vivo models of oxidative stress;
• Resveratrol as a potential effector of genoprotective pathways against hydrogen peroxide-induced DNA damage in astrocytes;
• Resveratrol effects vs. free radicals in human lymphocytes from bipolar disorder patients;
• Influence of epicatechin gallate over glial parameters: an in vitro study with rat C6 glioma cell line;
• Neuroprotective effects of epicatechin gallate in a 6-OHDA-induced parkinsonian in vivo model of Wistar rats.

3 - Peripheral receptors and neuroimmunomodulation.

Recent studies have revealed that key players in the generation of adaptive immune responses, dendritic cells (DCs) and lymphocytes, are capable of synthesizing and/or releasing classical neurotransmitters, including ACh, dopamine, 5-HT and glutamate. Disruption of the complex interactions between the nervous and immune systems, including the altered release of neurotransmitters, receptor expression or signal transduction, contributes to the pathogenesis of inflammatory and immune-mediated diseases. .

Aims:

• To study receptor-mediated signalling through neurotransmitters/immunomodulators in leukocytes;
• To characterize unidentified subpopulations of neurotransmitter-expressing leukocytes and/or specific transport systems in glutamatergic, serotoninergic, dopaminergic and colinergic routes.

Models:

Human-derived lymphocytes cultures and primary cultures isolated from different neural disease in vivo models.