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Published on: May 11, 2022
A combined cumulative threshold spectra and digital reconstruction analysis reveal structural alterations of
R Kongsui1, S J Johnson2, B A Graham3
1School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
Abstract:
Sickness behaviors have become the focus of great interest in recent years as they represent a clear case of how peripheral disturbances in immune signaling can disrupt quite complex behaviors. In the current study, we were interested in examining whether we could identify any significant morphological disturbances in microglia associated with these sickness-like behaviors in adult male Sprague-Dawley rats. We chose lipopolysaccharide (LPS 100 μg/kg/i.p.), to induce sickness-like behaviors as it is the most well-validated approach to do so in rodents and humans. We were particularly interested in examining changes in microglia within the prefrontal cortex (PFC) as several recent neuroimaging studies have highlighted significant functional changes in this region following peripheral LPS administration. Paraformaldehyde-fixed tissue was collected from animals 24h post LPS administration and labeled immunohistochemically with an antibody directed to bind to Iba-1, a protein known to be involved in the structural remodeling of microglia. To analyze changes, we have made use of two recently described image analysis procedures. The first is known as cumulative threshold spectra (CTS) analysis. The second involves the unsupervised digital reconstruction of microglia. We undertook these complementary analysis of microglial cells in the both the pre- and infralimbic divisions of the PFC. Our results indicated that microglial soma size was significantly enlarged, while cell processes had contracted slightly following LPS administration. To our knowledge this study is to first to definitely demonstrate substantial microglial disturbances within the PFC following LPS delivered at a dose that was sufficient to induce significant sickness-like behavior.
Insights
Peripheral immune signals can alter brain function, leading to sickness behaviors. This study found that lipopolysaccharide (LPS) administration caused significant microglial changes in the rat prefrontal cortex (PFC), correlating with sickness behaviors.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Sickness behaviors are triggered by peripheral immune system disturbances.
- Microglia, the brain's immune cells, are implicated in these behavioral changes.
- The prefrontal cortex (PFC) shows functional alterations following peripheral immune challenges.
Purpose of the Study:
- To investigate morphological changes in microglia within the PFC during sickness-like behaviors.
- To determine if lipopolysaccharide (LPS) induces specific microglial alterations in the PFC.
Main Methods:
- Adult male Sprague-Dawley rats were administered lipopolysaccharide (LPS) to induce sickness behaviors.
- Immunohistochemistry using an Iba-1 antibody was performed on PFC tissue 24 hours post-LPS.
- Microglial morphology was analyzed using cumulative threshold spectra (CTS) and unsupervised digital reconstruction.
Main Results:
- LPS administration significantly increased microglial soma size in the PFC.
- A slight contraction of microglial cell processes was observed post-LPS.
- These morphological changes occurred in both the prelimbic and infralimbic divisions of the PFC.
Conclusions:
- LPS induces significant and demonstrable morphological disturbances in microglia within the PFC.
- These findings link peripheral immune activation to specific microglial structural remodeling in a key brain region.
- This study provides the first definitive evidence of PFC microglial alterations associated with LPS-induced sickness behavior.
