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Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
Genetic Approaches Using Zebrafish to Study the Microbiota-Gut-Brain Axis in Neurological Disorders
Jae-Geun Lee1,2, Hyun-Ju Cho1, Yun-Mi Jeong1,3
1Disease Target Structure Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea.
Abstract:
The microbiota-gut-brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota-gut-brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer's disease.
Insights
The microbiota-gut-brain axis (MGBA) impacts brain health. Its dysfunction is linked to neurological disorders, and zebrafish offer a promising model to study these complex interactions.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- The microbiota-gut-brain axis (MGBA) is a complex bidirectional communication system linking gut microbes, the intestine, and the central nervous system.
- MGBA dysfunction, characterized by gut dysbiosis, contributes to gastrointestinal inflammation, immune cell infiltration in the brain, and neuroinflammation, impacting neurological function and behavior.
Purpose of the Study:
- To review current understanding of the MGBA's role in health and disease.
- To evaluate zebrafish as a model organism for studying MGBA mechanisms in neurological disorders.
Main Methods:
- Review of human and animal model studies on the MGBA.
- Analysis of zebrafish's molecular, genetic, and neurobehavioral traits relevant to MGBA research.
- Consideration of gnotobiotic approaches and in vivo imaging in zebrafish.
Main Results:
- The MGBA is crucial for nervous and gastrointestinal system development and physiology.
- Dysregulation of the MGBA is implicated in various neurological conditions, including autism spectrum disorder and Alzheimer's disease.
- Zebrafish present a valuable model for investigating MGBA mechanisms due to their genetic tractability and imaging capabilities.
Conclusions:
- The MGBA plays a significant role in both physiological and pathological conditions affecting the brain.
- Zebrafish, particularly when combined with gnotobiotic techniques and advanced imaging, offer a powerful platform for uncovering novel insights into microbiota-gut-brain interactions.
- Further research using zebrafish models holds promise for understanding and potentially treating neurological disorders linked to MGBA dysfunction.
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