BEHAVIOURAL AND NEUROCHEMICAL CONSEQUENCES OF CHRONIC GUT MICROBIOTA DEPLETION DURING ADULTHOOD IN THE RAT

被引：201

作者：

Hoban, A. E. ^{[1
,2
]}

Moloney, R. D. ^{[1
]}

Golubeva, A. V. ^{[1
]}

Neufeld, K. A. Mcvey ^{[1
]}

O'Sullivan, O. ^{[4
]}

Patterson, E. ^{[4
]}

Stanton, C. ^{[4
]}

Dinan, T. G. ^{[1
,3
]}

Clarke, G. ^{[1
,3
]}

Cryan, J. F. ^{[1
,2
]}

机构：

[1] Univ Coll Cork, APC Microbiome Inst, Cork, Ireland

[2] Univ Coll Cork, Dept Anat & Neurosci, Cork, Ireland

[3] Univ Coll Cork, Dept Psychiat & Neurobehav Sci, Cork, Ireland

[4] Teagasc Food Res Ctr, Moorepk, Cork, Ireland

来源：

NEUROSCIENCE | 2016年 / 339卷

基金：

爱尔兰科学基金会;

关键词：

gut microbiota; antibiotics; cognition; visceral sensitivity; brain monoamines; depressive-like behaviours; ANXIETY-LIKE BEHAVIOR; IRRITABLE-BOWEL-SYNDROME; TRKB MESSENGER-RNA; ADOLESCENT TESTOSTERONE; INTESTINAL MICROBIOTA; VISCERAL PAIN; BRAIN; STRESS; MICE; ANTIBIOTICS;

D O I：

10.1016/j.neuroscience.2016.10.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free (GF) mice highlight the extreme impact on brain health that results from life without commensal microbes. However, the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male Sprague-Dawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, increased visceral sensitivity and a greater display of depressive-like behaviours in the forced swim test. In tandem with these clear behavioural alterations we found changes in altered CNS serotonin concentration along with changes in the mRNA levels of corticotrophin releasing hormone receptor 1 and glucocorticoid receptor. Additionally, we found changes in the expression of brain derived neurotrophic factor (BDNF), a hallmark of altered microbiota-gut-brain axis signalling. In summary, this model of antibiotic-induced depletion of the gut microbiota can be used for future studies interested in the impact of the gut microbiota on host health without the confounding developmental influence of early-life microbial alterations. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：463 / 477

页数：15

共 73 条

[1] The effect of adolescent testosterone on hippocampal BDNF and TrkB mRNA expression: relationship with cell proliferation [J].

Allen, Katherine M. ;

Purves-Tyson, Tertia D. ;

Fung, Samantha J. ;

Weickert, Cynthia Shannon .

BMC NEUROSCIENCE, 2015, 16

[2]

[Anonymous], BRAIN BEHAV IMMUN

[3]

Arentsen Tim, 2015, Microbial Ecology in Health and Disease, V26, P29719, DOI 10.3402/mehd.v26.29719

[4] Human Microbiota-Associated Mice: A Model with Challenges [J].

Arrieta, Marie-Claire ;

Walter, Jens ;

Finlay, B. Brett .

CELL HOST & MICROBE, 2016, 19 (05) :575-578

[5] The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication [J].

Bercik, P. ;

Park, A. J. ;

Sinclair, D. ;

Khoshdel, A. ;

Lu, J. ;

Huang, X. ;

Deng, Y. ;

Blennerhassett, P. A. ;

Fahnestock, M. ;

Moine, D. ;

Berger, B. ;

Huizinga, J. D. ;

Kunze, W. ;

McLean, P. G. ;

Bergonzelli, G. E. ;

Collins, S. M. ;

Verdu, E. F. .

NEUROGASTROENTEROLOGY AND MOTILITY, 2011, 23 (12) :1132-E544

[6] The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice [J].

Bercik, Premysl ;

Denou, Emmanuel ;

Collins, Josh ;

Jackson, Wendy ;

Lu, Jun ;

Jury, Jennifer ;

Deng, Yikang ;

Blennerhassett, Patricia ;

Macri, Joseph ;

McCoy, Kathy D. ;

Verdu, Elena F. ;

Collins, Stephen M. .

GASTROENTEROLOGY, 2011, 141 (02) :599-U701

[7] Chronic Gastrointestinal Inflammation Induces Anxiety-Like Behavior and Alters Central Nervous System Biochemistry in Mice [J].

Bercik, Premysl ;

Verdu, Elena F. ;

Foster, Jane A. ;

Macri, Joseph ;

Potter, Murray ;

Huang, Xiaxing ;

Malinowski, Paul ;

Jackson, Wendy ;

Blennerhassett, Patricia ;

Neufeld, Karen A. ;

Lu, Jun ;

Khan, Waliul I. ;

Corthesy-Theulaz, Irene ;

Cherbut, Christine ;

Bergonzelli, Gabriela E. ;

Collins, Stephen M. .

GASTROENTEROLOGY, 2010, 139 (06) :2102-U409

[8] Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory' [J].

Bevins, Rick A. ;

Besheer, Joyce .

NATURE PROTOCOLS, 2006, 1 (03) :1306-1311

[9] Individual diet has sex-dependent effects on vertebrate gut microbiota [J].

Bolnick, Daniel I. ;

Snowberg, Lisa K. ;

Hirsch, Philipp E. ;

Lauber, Christian L. ;

Org, Elin ;

Parks, Brian ;

Lusis, Aldons J. ;

Knight, Rob ;

Caporaso, J. Gregory ;

Svanback, Richard .

NATURE COMMUNICATIONS, 2014, 5

[10] Microbiota and neurodevelopmental windows: implications for brain disorders [J].

Borre, Yuliya E. ;

O'Keeffe, Gerard W. ;

Clarke, Gerard ;

Stanton, Catherine ;

Dinan, Timothy G. ;

Cryan, John F. .

TRENDS IN MOLECULAR MEDICINE, 2014, 20 (09) :509-518

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