Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry

被引:314
作者
Sharma, S.
Fulton, S. [1 ,2 ]
机构
[1] CRCHUM, Dept Nutr, Montreal, PQ H1W 4A4, Canada
[2] Univ Montreal, Fac Med, Montreal Diabet Res Ctr, Montreal, PQ H1W 4A4, Canada
关键词
high-fat food; depression; anxiety; striatum; BDNF; CREB; ELEMENT-BINDING PROTEIN; NEUROTROPHIC FACTOR; NUCLEUS-ACCUMBENS; DELTA-FOSB; MOLECULAR-MECHANISMS; PALATABLE FOOD; DOPAMINE; BDNF; CREB; TRANSCRIPTION;
D O I
10.1038/ijo.2012.48
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: The biological mechanisms that link the development of depression to metabolic disorders such as obesity and diabetes remain obscure. Dopamine-and plasticity-related signalling in mesolimbic reward circuitry is implicated in the pathophysiology and aetiology of depression. OBJECTIVE: To determine the impact of a palatable high-fat diet (HFD) on depressive-like behaviour and biochemical alterations in brain reward circuitry in order to understand the neural processes that may contribute to the development of depression in the context of diet-induced obesity (DIO). METHODS: Adult male C57Bl6 mice were placed on a HFD or ingredient-matched, low-fat diet for 12 weeks. At the end of the diet regimen, we assessed anxiety and depressive-like behaviour, corticosterone levels and biochemical changes in the midbrain and limbic brain regions. Nucleus accumbens (NAc), dorsolateral striatum (DLS) and ventral tegmental area dissections were subjected to SDS-PAGE and immunoblotting using antibodies against D1A receptor, D2 receptor, brain-derived neurotrophic factor (BDNF), phospho-DARPP-32(thr75), phospho-CREB and Delta FosB. RESULTS: HFD mice showed significant decreases in open arm time and centre time activity in elevated plus maze and open field tasks, respectively, and increased immobility (behavioural despair) in the forced swim test. Corticosterone levels following acute restraint stress were substantially elevated in HFD mice. HFD mice had significantly higher D2R, BDNF and Delta FosB, but reduced D1R, protein expression in the NAc. Notably, the expression of BDNF in both the NAc and DLS and phospho-CREB in the DLS was positively correlated with behavioural despair. CONCLUSIONS: Our results demonstrate that chronic consumption of high-fat food and obesity induce plasticity-related changes in reward circuitry that are associated with a depressive-like phenotype. As increases in striatal BDNF and CREB activity are well implicated in depressive behaviour and reward, we suggest these signalling molecules may mediate the effects of high-fat feeding and DIO to promote negative emotional states and depressive-like symptomology. International Journal of Obesity (2013) 37, 382-389; doi:10.1038/ijo.2012.48; published online 17 April 2012
引用
收藏
页码:382 / 389
页数:8
相关论文
共 58 条
[1]   Mouse and rat BDNF gene structure and expression revisited [J].
Aid, Tamara ;
Kazantseva, Anna ;
Piirsoo, Marko ;
Palm, Kaia ;
Timmusk, Tonis .
JOURNAL OF NEUROSCIENCE RESEARCH, 2007, 85 (03) :525-535
[2]   DOPAMINE D1 RECEPTOR GENE EXPRESSION DECREASES IN THE NUCLEUS ACCUMBENS UPON LONG-TERM EXPOSURE TO PALATABLE FOOD AND DIFFERS DEPENDING ON DIET-INDUCED OBESITY PHENOTYPE IN RATS [J].
Alsio, J. ;
Olszewski, P. K. ;
Norback, A. H. ;
Gunnarsson, Z. E. A. ;
Levine, A. S. ;
Pickering, C. ;
Schioth, H. B. .
NEUROSCIENCE, 2010, 171 (03) :779-787
[3]  
[Anonymous], TRENDS NEUROSCI
[4]  
[Anonymous], AM J PHYSL ENDOCRINO
[5]   CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli [J].
Barrot, M ;
Olivier, JDA ;
Perrotti, LI ;
DiLeone, RJ ;
Berton, O ;
Eisch, AJ ;
Impey, S ;
Storm, DR ;
Neve, RL ;
Yin, JC ;
Zachariou, V ;
Nestler, EJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (17) :11435-11440
[6]   Regulation of anxiety and initiation of sexual behavior by CREB in the nucleus accumbens [J].
Barrot, M ;
Wallace, DL ;
Bolaños, CA ;
Graham, DL ;
Perrotti, LI ;
Neve, RL ;
Chambliss, H ;
Yin, JC ;
Nestler, EJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (23) :8357-8362
[7]   Role of Cdk5 in drug abuse and plasticity [J].
Benavides, DR ;
Bibb, JA .
CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY, 2004, 1025 :335-344
[8]   Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress [J].
Berton, O ;
McClung, CA ;
DiLeone, RJ ;
Krishnan, V ;
Renthal, W ;
Russo, SJ ;
Graham, D ;
Tsankova, NM ;
Bolanos, CA ;
Rios, M ;
Monteggia, LM ;
Self, DW ;
Nestler, EJ .
SCIENCE, 2006, 311 (5762) :864-868
[9]   New approaches to antidepressant drug discovery: beyond monoamines [J].
Berton, O ;
Nestler, EJ .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (02) :137-151
[10]   Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons [J].
Bibb, JA ;
Snyder, GL ;
Nishi, A ;
Yan, Z ;
Meijer, L ;
Fienberg, AA ;
Tsai, LH ;
Kwon, YT ;
Girault, JA ;
Czernik, AJ ;
Huganir, RL ;
Hemmings, HC ;
Nairn, AC ;
Greengard, P .
NATURE, 1999, 402 (6762) :669-671