LABORATORY OF NEUROBIOLOGY OF INVERTEBRATES

Research lines

Molecular bases of exhitation/inhibition imbalances in C. elegans

Excitatory and inhibitory neurotransmission is key to brain function. Imbalances in this system are linked to neuronal disorders, and the complexity of the mammalian nervous system makes studying these mechanisms difficult. The C. elegans neuromuscular system, in which both excitatory (cholinergic) and inhibitory (GABAergic) motor neurons regulate muscle contraction and relaxation, is an excellent platform to study the function, balance, and coordination between excitatory and inhibitory signals. We use genetic, pharmacological, behavioral, microscopic and optogenetic techniques to study the molecular basis of imbalances in some mutant genes linked to human disorders. We investigate the role of gendaf-18 (a human PTEN genortologue whose mutations have been reported in patients with Autism Spectrum Disorders) in neurodevelopment and E/I balance in C. elegans. We have explored how a diet rich in the ketone body beta-hydroxybutyrate can improve defects in this mutant (Giunti et al., 2023, Biorxiv). We are currently studying other genes associated with autism and other brain imbalance issues, and we are focused on exploring therapeutic alternatives to address these imbalances. Our aim is to contribute to the development of innovative therapeutic approaches and understand the molecular basis underlying some neural disorders. .

Nervous control of systemic processes in C. elegans

Animals, including humans, use neural control to respond to stress in the environment. A new study in C. elegans found that a brain-gut communication pathway involving tyramine regulates the release of insulin-like peptides to balance acute and long-term stress responses. The research aims to understand how the nervous system perceives nutritional status and its impact on adaptive strategies. These findings have implications for understanding stress response in mammals.

C. elegans: a platform for elucidating molecular mechanisms and potential chemotherapeutic strategies in diseases affecting the nervous system (NS).

The nematode C. elegans has become a valuable organism in studying the molecular mechanisms and potential treatments for diseases affecting the nervous system. With a complex mammalian nervous system consisting of billions of neurons and an intricate network of synapses, understanding neural circuits and neuronal function has proven challenging. However, C. elegans, with its well-established models for neurodegenerative disorders, provides a means to explore diseases of the nervous system. Neurodegenerative disorders, such as Huntington’s, Alzheimer’s, and Parkinson’s disease, are characterized by protein aggregation and cell death in neurons, ultimately leading to dysfunction. C. elegans models can accurately replicate protein aggregation, making it an effective tool for genetic and pharmacological screenings. Recent studies using C. elegans models have shown promising results, with identified compounds capable of modulating toxic aggregation. Our ultimate goal is the identification of new pharmacological targets and the development of therapeutic treatments for these disorders.