PUBLICATION
Simultaneous induction of systemic hyperglycaemia and stress impairs brain redox homeostasis in the adult zebrafish
- Authors
- Subba, R., Fasciolo, G., Geremia, E., Muscari Tomajoli, M.T., Petito, A., Carrella, S., Mondal, A.C., Napolitano, G., Venditti, P.
- ID
- ZDB-PUB-240721-6
- Date
- 2024
- Source
- Archives of biochemistry and biophysics 759: 110101 (Journal)
- Registered Authors
- Keywords
- NRF2, antioxidants, diabetes, distress, mitochondrial biogenesis, mitochondrial dynamics
- MeSH Terms
-
- Animals
- Antioxidants/metabolism
- Brain*/metabolism
- Glucose/metabolism
- Homeostasis*
- Hyperglycemia*/metabolism
- NF-E2-Related Factor 2*/metabolism
- Oxidation-Reduction*
- Oxidative Stress
- Reactive Oxygen Species*/metabolism
- Stress, Psychological/metabolism
- Zebrafish*
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 39029645 Full text @ Arch. Biochem. Biophys.
Citation
Subba, R., Fasciolo, G., Geremia, E., Muscari Tomajoli, M.T., Petito, A., Carrella, S., Mondal, A.C., Napolitano, G., Venditti, P. (2024) Simultaneous induction of systemic hyperglycaemia and stress impairs brain redox homeostasis in the adult zebrafish. Archives of biochemistry and biophysics. 759:110101.
Abstract
For diabetic patients it is crucial to constantly monitor blood glucose levels to mitigate complications due to hyperglycaemia, including neurological issues and cognitive impairments. This activity leads to psychological stress, called "diabetes distress," a problem for most patients living with diabetes. Diabetes distress can exacerbate the hyperglycaemia effects on brain and negatively impact the quality of life, but the underlying mechanisms remain poorly explored. We simulated diabetes distress in adult zebrafish by modelling hyperglycaemia, through exposure to dextrose solution, along with chronic unpredictable mild stress (CUMS), and evaluated brain redox homeostasis by assessing reactive oxygen species (ROS) content, the antioxidant system, and effects on mitochondrial biogenesis and fission/fusion processes. We also evaluated the total, cytosolic and nuclear content of nuclear factor erythroid 2-related factor 2 (NRF2), a critical regulator of redox balance, in the whole brain and total NRF2 in specific brain emotional areas. The combined CUMS+Dextrose challenge, but not the individual treatments, reduced total NRF2 levels in the entire brain, but strongly increased its levels in the nuclear fraction. Compensatory upregulation of antioxidant genes appeared inadequate to combat elevated levels of ROS, leading to lowering of the reduced glutathione content and total antioxidant capacity. CUMS+Dextrose treatment also upregulated transcription factors implicated in mitochondrial biogenesis and dynamics with a predominance of fission, which is consistent with increased oxidative stress. In conclusion, this study highlights the close interplay between hyperglycaemia and psychological distress causing overriding oxidative stress in the brain, rendering the organism vulnerable to the development of disease complications.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping