Skip to main content

ORIGINAL RESEARCH article

Front. Comput. Neurosci.
Volume 18 - 2024 | doi: 10.3389/fncom.2024.1386841

Simulating combined monoaminergic depletions in a PD animal model through a bio-constrained differential equations system

Provisionally accepted
Samuele Carli Samuele Carli 1Sebastian Luca D'addario Sebastian Luca D'addario 2Luigi Brugnano Luigi Brugnano 3Daniele Caligiore Daniele Caligiore 1*
  • 1 National Research Council (CNR), Roma, Lazio, Italy
  • 2 Santa Lucia Foundation (IRCCS), Rome, Lazio, Italy
  • 3 University of Florence, Florence, Tuscany, Italy

The final, formatted version of the article will be published soon.

    Historically, Parkinson's Disease (PD) research focused on dopamine-producing cell dysfunction in the substantia nigra pars compacta, linked to motor regulation in the basal ganglia. Therapies have mainly aimed at restoring dopamine (DA) R levels, showing effectiveness but variable outcomes and side effects. Recent evidence indicates PD complexity, implicating disruptions in DA, noradrenaline (NA), and serotonin (5-HT) R systems, possibly underlying the variations in therapy effects. We present a system-level bio-constrained computational model that comprehensively investigates the dynamic interactions between these systems R . The model successfully replicates experimental data demonstrating the impact of NA and 5-HT depletion in a PD animal model, shedding light on potential causal relationships between basal ganglia regions and neuromodulator release areas. The model generates predictions regarding changes in other unexplored brain regions, suggesting avenues for further investigation. It also highlights the potential efficacy of alternative treatments targeting the locus coeruleus and dorsal raphe nucleus, yet these are preliminary findings whose effectiveness needs further validation. R Sensitivity analysis identifies critical model parameters, offering insights into key factors influencing brain area activity. A stability analysis underscores the robustness of our mathematical formulation, bolstering the model validity. Our holistic approach emphasizes that PD is a multifactorial disorder and opens promising avenues for early diagnosis tools harnessing the intricate interactions among monoaminergic systems. Investigating NA and 5-HT systems alongside the DA system may yield more effective, subtype-specific therapies R . The exploration of multisystem dysregulation in PD is poised to revolutionize our understanding and management of this complex neurodegenerative disorder.

    Keywords: Parkinson's disease, Treatment, Serotonin, noradrenaline, computational model, network neuroscience

    Received: 16 Feb 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Carli, Luca D'addario, Brugnano and Caligiore. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Daniele Caligiore, National Research Council (CNR), Roma, 00185, Lazio, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.