PMID- 32240763 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20211107 IS - 1090-2139 (Electronic) IS - 0889-1591 (Print) IS - 0889-1591 (Linking) VI - 88 DP - 2020 Aug TI - Obesogenic diet-associated C-reactive protein predicts reduced central dopamine and corticostriatal functional connectivity in female rhesus monkeys. PG - 166-173 LID - S0889-1591(19)31625-3 [pii] LID - 10.1016/j.bbi.2020.03.030 [doi] AB - Alterations in dopamine (DA) signaling and reductions in functional connectivity (FC; a measure of temporal correlations of activity between different brain regions) within dopaminergic reward pathways are implicated in the etiology of psychopathology and have been associated with increased concentrations of inflammatory markers, including C-reactive protein. Peripheral and central inflammatory cytokines that have been shown to disrupt DA signaling and corticostriatal FC are associated with C-reactive protein, an acute phase reactant that is used translationally as a marker of systemic inflammation. One factor that can significantly increase systemic inflammation to produce neuroadaptations in reward pathways is a diet that results in fat mass accumulation (e.g. obesogenic diet). The current study in female rhesus monkeys maintained in a standard laboratory chow (n = 18) or on obesogenic diet (n = 16) for 12-months tested the hypothesis that an obesogenic diet would alter central DA and homovanillic acid (HVA) concentrations, and be associated with increased CRP concentrations and decreased FC between corticostriatal regions at 12-months following dietary intervention. We specifically assessed FC between the nucleus accumbens (NAcc) and two sub-regions of the prefrontal cortex (PFC) previously associated with CRP concentrations, the ventromedial PFC (vmPFC) and the orbitofrontal cortex (OFC), which are also involved in emotional and motivational salience assessment, and in goal-directed behavior, impulse control and the salience/value of food, respectively. Results showed that CSF DA concentrations were decreased (p = 0.002), HVA:DA ratios were increased (p = 0.016), and body mass index was increased (p = 0.047) over the 12-months of consuming an obesogenic diet. At 12-months, females maintained in the obesogenic diet exhibited higher CRP concentrations than females consuming chow-only (p = 0.008). Linear regression analyses revealed significant CRP by dietary condition interactions on DA concentrations (beta = -5.10; p = 0.017) and HVA:DA ratios (beta = 5.14; p = 0.029). Higher CRP concentrations were associated with lower CSF DA concentrations (r = -0.69; p = 0.004) and greater HVA:DA ratios only in females maintained in the obesogenic dietary condition (r = 0.58; p = 0.024). Resting-state magnetic resonance neuroimaging (rs-fMRI) in a subset of females from each diet condition (n = 8) at 12-months showed that higher CRP concentrations were associated decreased FC between the NAcc and subregions of the prefrontal cortex (PFC; p's < 0.05). Decreased FC between the NAcc and PFC subregions were also associated with lower concentrations of DA and greater HVA:DA ratios (p's < 0.05). Overall, these data suggest that increased inflammatory signaling driving heightened CRP levels may mediate the adverse consequences of obesogenic diets on DA neurochemistry and corticostriatal connectivity. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Godfrey, Jodi R AU - Godfrey JR AD - Yerkes National Primate Research Center, Atlanta, GA, United States. FAU - Pincus, Melanie AU - Pincus M AD - Yerkes National Primate Research Center, Atlanta, GA, United States. FAU - Kovacs-Balint, Zsofia AU - Kovacs-Balint Z AD - Yerkes National Primate Research Center, Atlanta, GA, United States. FAU - Feczko, Eric AU - Feczko E AD - Department Of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States. FAU - Earl, Eric AU - Earl E AD - Department Of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States. FAU - Miranda-Dominguez, Oscar AU - Miranda-Dominguez O AD - Department Of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States. FAU - Fair, Damien A AU - Fair DA AD - Department Of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States. FAU - Jones, Sara R AU - Jones SR AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, United States. FAU - Locke, Jason AU - Locke J AD - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, United States. FAU - Sanchez, Mar M AU - Sanchez MM AD - Yerkes National Primate Research Center, Atlanta, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. FAU - Wilson, Mark E AU - Wilson ME AD - Yerkes National Primate Research Center, Atlanta, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. FAU - Michopoulos, Vasiliki AU - Michopoulos V AD - Yerkes National Primate Research Center, Atlanta, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: vmichop@emory.edu. LA - eng GR - P50 AA026117/AA/NIAAA NIH HHS/United States GR - R38 AI140299/AI/NIAID NIH HHS/United States GR - P51 OD011132/OD/NIH HHS/United States GR - R01 DK096983/DK/NIDDK NIH HHS/United States GR - R01 DA048490/DA/NIDA NIH HHS/United States GR - K12 HD085850/HD/NICHD NIH HHS/United States GR - U54 AG062334/AG/NIA NIH HHS/United States GR - U01 AA014091/AA/NIAAA NIH HHS/United States GR - P50 DA006634/DA/NIDA NIH HHS/United States GR - T32 DA041349/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200330 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 9007-41-4 (C-Reactive Protein) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - *C-Reactive Protein MH - Diet MH - *Dopamine MH - Female MH - Macaca mulatta MH - Nucleus Accumbens MH - Reward PMC - PMC7416544 MID - NIHMS1581700 OTO - NOTNLM OT - Diet OT - Dopamine OT - Inflammation OT - Reward pathways COIS- Disclosures All authors have no conflicts of interest to disclose. EDAT- 2020/04/03 06:00 MHDA- 2021/04/28 06:00 PMCR- 2021/08/01 CRDT- 2020/04/03 06:00 PHST- 2019/12/30 00:00 [received] PHST- 2020/03/27 00:00 [revised] PHST- 2020/03/28 00:00 [accepted] PHST- 2020/04/03 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/04/03 06:00 [entrez] PHST- 2021/08/01 00:00 [pmc-release] AID - S0889-1591(19)31625-3 [pii] AID - 10.1016/j.bbi.2020.03.030 [doi] PST - ppublish SO - Brain Behav Immun. 2020 Aug;88:166-173. doi: 10.1016/j.bbi.2020.03.030. Epub 2020 Mar 30.