Recentincreasesintheepidemicsofobesity,diabetes,andbotheatingandgastrointestinal(GI)disordersunderscore thefactthatadequatetreatmentshaveyettobedeveloped.AstheNIHBRAINinitiativeandotherprogramshave stressed,theunderlyingbrain?gutcircuitrymustbecharacterizedifclinicalinterventionsaretobedevelopedefficiently. Theoverallgoalofthecurrentresearchprogramistousestate?of?the?artneuroscienceprotocolstocharacterizethose brain?gutpathways.Whilethepresentprojecthasmadeimportantprogressdelineatingtheautonomicprojectionsto theoutersmoothmusclewalloftheesophagus,stomach,andintestines,characterizationsoftheelementsofvagaland otherautonomiccircuitrythatinnervatetheinnermucosalandsubmucosalliningsoftheintestineshaveyettobe accomplished.Thislackofinformationfortheinnerwalloftheintestinesisproblematic,sincethevagalsensory innervationofthemucosalliningoftheGItractisfundamentalforintegratingtheinformationandpatternsofnutrient fluxes,caloricdensities,paracrinesignaling,andmicrobiomedynamicsthatcollectivelycontrolingestion,digestion, absorption,andmetabolismofnutrients.IntwocomplementaryseriesofexperimentsorganizedastwoSpecificAims, thepresentrenewalrequestproposestogeneratecomprehensivefoundationaldescriptionsofthevagalsensory projectionstothemucosaandsubmucosaoftheintestines.
SpecificAim1 proposesasetofsixcumulativeexperiments tophenotype,determine3Darchitecturalmorphometry,maptopographically,andestablishthesurgicalapproachto therecentlydescribedvagalcryptendingsthatinnervatetheintestinalglands.SA1willalsocomparethemorphology ofthecryptendingsinmalesandfemalesandassessremodelingoftheendingsasafunctionofmaintenanceonan obesogenichighfatdiet.
SpecificAim2 proposesaparallelsetofexperimentschacterizingthephenotype,3D morphometry,maps,andvagalpathwaysofthevagalvillusarborsthatinnervatetheepithelialwallsofintestinalvilli.In sum,thepresentprojectwillprovidefundamentalobservationsonthesensoryelementsofthebrain?intestinesaxisthat areimmediatelyinvolvedinintegratingtheGIsignalscontrollingmetabolism.

Public Health Relevance

Thepresentprojectwillinventoryandmapforthefirsttimethosebrain?gutneuralcircuitsintheintestines,specifically inthemucosaandsubmucosa,thatcontrolthedigestion,absorption,andmetabolismoffood.Theneuronal phenotypesandtaxonomicmapsofthecircuitrywillsupplyfoundationalinformationneededtodesignandrefine clinicalinterventionstotreatobesity,diabetes,andamyriadofeatingdisorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK027627-39
Application #
9418589
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Greenwel, Patricia
Project Start
1980-01-01
Project End
2021-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
39
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Purdue University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Ulusoy, Ayse; Phillips, Robert J; Helwig, Michael et al. (2017) Brain-to-stomach transfer of ?-synuclein via vagal preganglionic projections. Acta Neuropathol 133:381-393
Powley, Terry L; Hudson, Cherie N; McAdams, Jennifer L et al. (2016) Vagal Intramuscular Arrays: The Specialized Mechanoreceptor Arbors That Innervate the Smooth Muscle Layers of the Stomach Examined in the Rat. J Comp Neurol 524:713-37
Walter, Gary C; Phillips, Robert J; McAdams, Jennifer L et al. (2016) Individual sympathetic postganglionic neurons coinnervate myenteric ganglia and smooth muscle layers in the gastrointestinal tract of the rat. J Comp Neurol 524:2577-603
Powley, Terry L; Hudson, Cherie N; McAdams, Jennifer L et al. (2014) Organization of vagal afferents in pylorus: mechanoreceptors arrayed for high sensitivity and fine spatial resolution? Auton Neurosci 183:36-48
Phillips, Robert J; Billingsley, Cherie N; Powley, Terry L (2013) Macrophages are unsuccessful in clearing aggregated alpha-synuclein from the gastrointestinal tract of healthy aged Fischer 344 rats. Anat Rec (Hoboken) 296:654-69
Powley, Terry L; Baronowsky, Elizabeth A; Gilbert, Jared M et al. (2013) Vagal afferent innervation of the lower esophageal sphincter. Auton Neurosci 177:129-42
Phillips, Robert J; Hudson, Cherie N; Powley, Terry L (2013) Sympathetic axonopathies and hyperinnervation in the small intestine smooth muscle of aged Fischer 344 rats. Auton Neurosci 179:108-21
Phillips, R J; Martin, F N; Billingsley, C N et al. (2013) Alpha-synuclein expression patterns in the colonic submucosal plexus of the aging Fischer 344 rat: implications for biopsies in aging and neurodegenerative disorders? Neurogastroenterol Motil 25:e621-33
Powley, Terry L; Mittal, Ravinder K; Baronowsky, Elizabeth A et al. (2013) Architecture of vagal motor units controlling striated muscle of esophagus: peripheral elements patterning peristalsis? Auton Neurosci 179:90-8
Phillips, Robert J; Powley, Terry L (2012) Macrophages associated with the intrinsic and extrinsic autonomic innervation of the rat gastrointestinal tract. Auton Neurosci 169:12-27

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