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Jonathan Lendrum*, 1
Bradley Seebach, 1
Barrett Klein, 2
Andrew Berns, 1
Sumei Liu
1
Department of Biology, 2
Department of Computer Science, University of Wisconsin-La Crosse, La
Crosse, WI 54601
Presentation Type: Oral Presentation, Presentation Location: Nov. 7th
2015 @ 1:00pm in RC 127
ABSTRACT:
Throughout human history, the purpose of sleep has been at the center of existential enigmas. Newborns
sleep an astounding 14 to 17 hours a day; and as adults, we require nearly 1/3 of our lives to be spent
asleep. The glymphatic system, a recently discovered, water-based drainage system for neural tissues that
is active during sleep phases—but inactive during periods of wakefulness—offers strong evidence for the
evolutionary importance of mammalian sleep. When we sleep, the glymphatic system functions as a sink
for our dirty brains; using watery cerebrospinal fluid to wash away harmful extracellular waste products
(such as beta-amyloid associated with Alzheimer’s disease) that accumulates in the compact spaces of
highly sensitive brain tissues during waking hours. In this way, a good night’s sleep may literally clear the
mind, a property likely responsible for the restorative properties of sleep. Furthermore, in the last decade
mounting evidence suggests complex interactions between hosts and their microbial communities, known
as the microbiota-gut-brain axis, play a critical role determining health and disease states. Our present
study investigates multiple relationships between altered compositions of intestinal microbiota and sleep
behavior in a pilot study using fifteen male (C57BL/6) mice. During summer 2015, three groups of five
mice were individually housed in cages custom-fitted with an infrared video surveillance system. We then
gavaged five of the mice with a broad-spectrum antibiotic cocktail consisting of ampicillin, neomycin,
metronidazole and vancomycin to deplete gut microbiota. To a second group of five mice we used high-
fat (60% kcal) diet feeding, which has been shown to significantly alter bacterial compositions in the gut.
The final five mice served as the control group and were fed a content-matched low fat diet. By
sequencing the genomes of the remaining microbes, we can relate changes in gut permeability, aquaporin-
4 expression and the video-recorded sleep behavior to certain populations of gut bacteria. The discovery
of the glymphatic system and improving knowledge of the microbiota-gut-brain axis provides a possible,
explanatory link for how and why bacterial populations may regulate sleep phases, and why reduction in
the diversity of bacteria in the gut (as a result of poor nutrition, or antibiotic exposure)
	
  
Induction	
  of	
  intestinal	
  dysbiosis	
  through	
  broad-­‐spectrum	
  antibiotic	
  gavage,	
  
high-­‐fat	
  feeding:	
  effects	
  on	
  the	
  microbiota-­‐gut-­‐brain	
  axis	
  and	
  sleep	
  function	
  
in	
  C57BL/6	
  mice

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Microbiota-Gut-Brain Axis, Glymphatic System and Sleep

  • 1. 1 Jonathan Lendrum*, 1 Bradley Seebach, 1 Barrett Klein, 2 Andrew Berns, 1 Sumei Liu 1 Department of Biology, 2 Department of Computer Science, University of Wisconsin-La Crosse, La Crosse, WI 54601 Presentation Type: Oral Presentation, Presentation Location: Nov. 7th 2015 @ 1:00pm in RC 127 ABSTRACT: Throughout human history, the purpose of sleep has been at the center of existential enigmas. Newborns sleep an astounding 14 to 17 hours a day; and as adults, we require nearly 1/3 of our lives to be spent asleep. The glymphatic system, a recently discovered, water-based drainage system for neural tissues that is active during sleep phases—but inactive during periods of wakefulness—offers strong evidence for the evolutionary importance of mammalian sleep. When we sleep, the glymphatic system functions as a sink for our dirty brains; using watery cerebrospinal fluid to wash away harmful extracellular waste products (such as beta-amyloid associated with Alzheimer’s disease) that accumulates in the compact spaces of highly sensitive brain tissues during waking hours. In this way, a good night’s sleep may literally clear the mind, a property likely responsible for the restorative properties of sleep. Furthermore, in the last decade mounting evidence suggests complex interactions between hosts and their microbial communities, known as the microbiota-gut-brain axis, play a critical role determining health and disease states. Our present study investigates multiple relationships between altered compositions of intestinal microbiota and sleep behavior in a pilot study using fifteen male (C57BL/6) mice. During summer 2015, three groups of five mice were individually housed in cages custom-fitted with an infrared video surveillance system. We then gavaged five of the mice with a broad-spectrum antibiotic cocktail consisting of ampicillin, neomycin, metronidazole and vancomycin to deplete gut microbiota. To a second group of five mice we used high- fat (60% kcal) diet feeding, which has been shown to significantly alter bacterial compositions in the gut. The final five mice served as the control group and were fed a content-matched low fat diet. By sequencing the genomes of the remaining microbes, we can relate changes in gut permeability, aquaporin- 4 expression and the video-recorded sleep behavior to certain populations of gut bacteria. The discovery of the glymphatic system and improving knowledge of the microbiota-gut-brain axis provides a possible, explanatory link for how and why bacterial populations may regulate sleep phases, and why reduction in the diversity of bacteria in the gut (as a result of poor nutrition, or antibiotic exposure)   Induction  of  intestinal  dysbiosis  through  broad-­‐spectrum  antibiotic  gavage,   high-­‐fat  feeding:  effects  on  the  microbiota-­‐gut-­‐brain  axis  and  sleep  function   in  C57BL/6  mice