This preprint is under consideration at Journal of Neuroinflammation. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice
Shun-Fen Tzeng
National Cheng Kung University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0558-8205
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Consecutive peripheral immune challenges can modulate the responses of brain resident microglia to stimuli. High-fat diet (HFD) intake has been reported to stimulate the activation of astrocytes and microglia in the arcuate nucleus (ARC) of the hypothalamus in obese rodents and humans. However, it is unknown whether intermittent exposure to additional peripheral immune challenge can modify HFD-induced hypothalamic glial activation in obese individuals.
Methods: In this study, we administered 1 mg/kg LPS (or saline) by intraperitoneal (i.p.) injection to 8-week-old male mice after 1, 2, or 8 weeks of a regular diet (show) or HFD. The level of interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) expression in the plasma and hypothalamic tissue was analyzed 24 h after each LPS injection. The behaviors of the animals in the four groups (the chow-saline, chow-LPS, HFD-saline, and HFD-LPS groups) were examined 5 months after exposure to chow or a HFD. Morphological examination of microglia in related brain regions was also conducted.
Results: The plasma levels and hypothalamic mRNA levels of IL-1b and TNF-a were significantly upregulated 24 h after the first injection of LPS but not after the second or third injection of LPS. Chow-LPS mice displayed increased exploratory behavior 5 months after feeding. However, this LPS-induced abnormal exploratory behavior was inhibited in HFD-fed mice. Chronic HFD feeding for 5 months induced apparent increases in the number and cell body size of microglia, mainly in the ARC, and also increased the size of microglia in the NAc and insula. Moreover, microglial activation in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), insula, and basolateral amygdala (BLA) was observed in chow-LPS mice. However, microglial activation in the analyzed brain regions was suppressed in HFD-LPS mice.
Conclusions: Altogether, the results indicate that intermittent peripheral challenge with LPS might prime microglia in the ARC and NAc to modify their response to chronic HFD feeding. Alternatively, chronic HFD feeding might mediate microglia in LPS-affected brain regions and subsequently suppress LPS-induced atypical exploratory behavior. Our findings suggest that the interaction of intermittent acute peripheral immune challenges with chronic HFD intake can drive microglia to amend the microenvironment and further modify animal behaviors in the later life.
Keywords
peripheral inflammation, obesity, microglia, gliosis, exploration
Figure 1
Figure 2
Figure 3
Figure 4
.jpg?maxDims=150x150)
Figure 5
Figure 6
.tif?maxDims=150x150)
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 13 Apr, 2020
No community comments so far
Review #2 received
Received 24 Apr, 2020
Review #1 received
Received 21 Apr, 2020
Reviewer #2 agreed
On 17 Apr, 2020
Reviewers invited
Invitations sent on 15 Apr, 2020
Reviewer #1 agreed
On 15 Apr, 2020
Editor invited
On 07 Apr, 2020
Editor assigned
On 07 Apr, 2020
Submission checks complete
On 06 Apr, 2020
No comments provided
Editorial decision: Major Revision
On 01 Mar, 2020
Review #2 received
Received 27 Feb, 2020
Review #1 received
Received 24 Feb, 2020
Reviewer #2 agreed
On 11 Feb, 2020
Reviewer #1 agreed
On 10 Feb, 2020
Reviewers invited
Invitations sent on 09 Feb, 2020
Editor assigned
On 05 Feb, 2020
First submitted
On 04 Feb, 2020
Submission checks complete
On 04 Feb, 2020
Editor invited
On 04 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
Learn more about our company.
This preprint is under consideration at Journal of Neuroinflammation. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Intermittent peripheral exposure to lipopolysaccharide induces exploratory behavior in mice and regulates brain glial activity in obese mice
Shun-Fen Tzeng
National Cheng Kung University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0558-8205
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 13 Apr, 2020
No community comments so far
Review #2 received
Received 24 Apr, 2020
Review #1 received
Received 21 Apr, 2020
Reviewer #2 agreed
On 17 Apr, 2020
Reviewers invited
Invitations sent on 15 Apr, 2020
Reviewer #1 agreed
On 15 Apr, 2020
Editor invited
On 07 Apr, 2020
Editor assigned
On 07 Apr, 2020
Submission checks complete
On 06 Apr, 2020
No comments provided
Editorial decision: Major Revision
On 01 Mar, 2020
Review #2 received
Received 27 Feb, 2020
Review #1 received
Received 24 Feb, 2020
Reviewer #2 agreed
On 11 Feb, 2020
Reviewer #1 agreed
On 10 Feb, 2020
Reviewers invited
Invitations sent on 09 Feb, 2020
Editor assigned
On 05 Feb, 2020
First submitted
On 04 Feb, 2020
Submission checks complete
On 04 Feb, 2020
Editor invited
On 04 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Consecutive peripheral immune challenges can modulate the responses of brain resident microglia to stimuli. High-fat diet (HFD) intake has been reported to stimulate the activation of astrocytes and microglia in the arcuate nucleus (ARC) of the hypothalamus in obese rodents and humans. However, it is unknown whether intermittent exposure to additional peripheral immune challenge can modify HFD-induced hypothalamic glial activation in obese individuals.
Methods: In this study, we administered 1 mg/kg LPS (or saline) by intraperitoneal (i.p.) injection to 8-week-old male mice after 1, 2, or 8 weeks of a regular diet (show) or HFD. The level of interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) expression in the plasma and hypothalamic tissue was analyzed 24 h after each LPS injection. The behaviors of the animals in the four groups (the chow-saline, chow-LPS, HFD-saline, and HFD-LPS groups) were examined 5 months after exposure to chow or a HFD. Morphological examination of microglia in related brain regions was also conducted.
Results: The plasma levels and hypothalamic mRNA levels of IL-1b and TNF-a were significantly upregulated 24 h after the first injection of LPS but not after the second or third injection of LPS. Chow-LPS mice displayed increased exploratory behavior 5 months after feeding. However, this LPS-induced abnormal exploratory behavior was inhibited in HFD-fed mice. Chronic HFD feeding for 5 months induced apparent increases in the number and cell body size of microglia, mainly in the ARC, and also increased the size of microglia in the NAc and insula. Moreover, microglial activation in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), insula, and basolateral amygdala (BLA) was observed in chow-LPS mice. However, microglial activation in the analyzed brain regions was suppressed in HFD-LPS mice.
Conclusions: Altogether, the results indicate that intermittent peripheral challenge with LPS might prime microglia in the ARC and NAc to modify their response to chronic HFD feeding. Alternatively, chronic HFD feeding might mediate microglia in LPS-affected brain regions and subsequently suppress LPS-induced atypical exploratory behavior. Our findings suggest that the interaction of intermittent acute peripheral immune challenges with chronic HFD intake can drive microglia to amend the microenvironment and further modify animal behaviors in the later life.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8