Study of Metabolic Alterations in the Gut-Brain Axis Induced by Neuroprotective and Neurotoxic Compounds in Drosophila melanogaster

• Grant number: 25/05314-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Marina Piacenti da Silva
• Grantee: Luísa de Toledo Tury
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil
• Associated research grant: 24/10984-2 - Investigation of Neurodegenerative Mechanisms Associated with Environmental Factors, AP.R

Abstract

Neurodegenerative diseases represent an increasing public health challenge, and the fundamental role of the gut-brain axis in their pathogenesis is becoming increasingly clear. This project proposes to study the metabolic changes induced by neuroprotective compounds - acetate and curcumin - and neurotoxic compounds - heavy metals and magnesium oxide (MgO) nanoparticles - in Drosophila melanogaster, an in vivo model whose gut microbiota, although simple, shares functional similarities with that of mammals. Different exposure groups will be tested: a negative control, a positive control (lead exposure), and treatments with acetate, MgO, curcumin, and a group receiving a combination of MgO and curcumin. To assess neurodegenerative aspects, lifespan assays, negative geotaxis tests to evaluate locomotor and cognitive functions, and colony forming unit counts to characterize the gut microbiota will be performed. In addition, liquid chromatography coupled to mass spectrometry (LC-MS) will be used to quantify essential metabolites such as neurotransmitters (glutamate, GABA, dopamine, acetylcholine) and short-chain fatty acids. Our hypothesis is that neuroprotective compounds may favorably modulate the metabolic profiles of the microbiota and attenuate neurodegenerative processes, while neurotoxic agents may exacerbate metabolic imbalances and negatively impact behavior and survival. The results aim to elucidate the interactions of these metabolites within the gut-brain axis and contribute to the understanding and development of new therapeutic strategies for neurodegenerative diseases.