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UC San Diego UC San Diego Electronic Theses and Dissertations Title Nod1/Nod2 Receptors Modulate the Microbiota-Gut-Brain Axis Permalink https://escholarship.org/uc/item/7df946db Author Schneider, Melinda A. Publication Date 2015 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY  OF  CALIFORNIA,  SAN  DIEGO               Nod1/Nod2  Receptors  Modulate  the  Microbiota-­‐Gut-­‐Brain  Axis                   A  thesis  submitted  in  partial  satisfaction  of  the  requirements     for  the  degree  of  Master  of  Science     in     Biology             by     Melinda  A.  Schneider         Committee  in  charge:         Professor  Melanie  Gareau,  Chair     Professor  Nigel  Crawford,  Co-­‐Chair   Professor  Kim  Barrett   Professor  Jill  Leutgeb       2015 Copyright     Melinda  A.  Schneider,  2015     All  rights  reserved.     ii The  thesis  of  Melinda  A.  Schneider  is  approved  and  is  acceptable  in  quality  and   form  for  electronic  and  microfilm  publication:       __________________________________________________________________________________________       __________________________________________________________________________________________       __________________________________________________________________________________________          Co-­‐Chair               __________________________________________________________________________________________                  Chair                                                             University  of  California,  San  Diego     2015         iii DEDICATION     I  dedicate  this  thesis  to  Cindy  and  Doug  for  their  love,  encouragement  and  support,   and  to  Jenny  who  can  always  make  me  laugh.   iv EPIGRAPH   Dancing  in  all  its  forms  cannot  be  excluded  from  the  curriculum  of  all  noble   education;  dancing  with  the  feet,  with  ideas,  with  words,  and,  need  I  add  that   one  must  also  be  able  to  dance  with  the  pen?       Nietzsche   v TABLE  OF  CONTENTS     Signature  Page…………………………………………………………………….…..              iii   Dedication………………………………………………………………………….…..                iv   Epigraph…………………………………………………………………………………                v   Table  of  Contents……………………………………………………………………                vi   List  of  Figures…………………………………………………………………………              vii   List  of  Illustrations………………………………………………………………….            viii   List  of  Tables…………………………………………………………………………..              ix   Acknowledgements…………………………………………………………………                x   Abstract  of  the  Thesis…………………………………..………………………….              xi   I. Introduction……………………………………………………………………………                1   II. Materials  and  Methods…………………………………………………………….            16   III. Results……………………………………………………………………………………            24   IV. Discussion………………………………………………………………………………            38   V. Appendix:  Illustrations  and  Tables…………………………………………..            48   References………………………………………………………………………………          52   vi LIST  OF  FIGURES     Figure  1:  NodDKO  mice  display  anxiety-­‐like  behavior  and  cognitive     deficits  compared  to  C57BL/6  controls  …………………………………………          28     Figure  2:  Dysbiosis  was  observed  in  NodDKO  mice  compared  to   C57BL/6  controls,  which  was  normalized  by  co-­‐housing  strategies.…        30     Figure  3:  Changes  in  behavior  in  NodDKO  mice  were  not  restored     upon  co-­‐housing  with  C57BL/6  mice  ……………………………………………          33     Figure  4:  Elevated  serum  corticosterone  level  indicates  increased     activation  of  the  HPA  axis  in  NodDKO  mice    …………………………………          36   vii LIST  OF  ILLUSTRATIONS   Illustration  1:  Water  Avoidance  Stress  (WAS)  Setup………………...…………            49   Illustration  2:  Light/Dark  Box  Test  Apparatus  ……..……………………………            49   Illustration  3:  Novel  Object  Recognition  (NOR)  Test  ……………………..……..            50     viii LIST  OF  TABLES     Table  1:  Primer  sequences  employed  in  qPCR  analysis  of  the     microbiota  .……………………………………………………………………………..          51     ix

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1. I. INTRODUCTION main bacterial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria,. Verrocomicrobia and Fusobacteria. (Zhang more diverse microbiota, but performed better in behavioral cognition tests (i.e..
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