title: Quantitative Proteomic Analysis of the Orbital Frontal Cortex in Rats Following Extended Exposure to Caffeine Reveals Extensive Changes to Protein Expression: Implications for Neurological Disease.
abstract: Caffeine is a plant-derived psychostimulant and a common additive found in a wide range of foods and pharmaceuticals. The orbitofrontal cortex (OFC) is rapidly activated by flavours, integrates gustatory and olfactory information, and plays a critical role in decision-making, with dysfunction contributing to psychopathologies and neurodegenerative conditions. This study investigated whether long-term consumption of caffeine causes changes to behavior and protein expression in the OFC. Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 0.6 g/L caffeine solution. Locomotor behavior was measured on the first and last day of treatment, then again after 9 days treatment free following exposure to a mild stressor. When tested drug free, caffeine-treated animals were hyperactive compared to controls. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free shotgun proteomics found 157 proteins differentially expressed in the caffeine-drinking rats compared to control. Major proteomic effects were seen for cell-to-cell communication, cytoskeletal regulation, and mitochondrial function. Similar changes have been observed in neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia.
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Franklin
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mirzaei
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Wearne
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Judi
authors.initials: J
authors.lastname: Homewood
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Ann K
authors.initials: AK
authors.lastname: Goodchild
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Haynes
authors.affiliation: Department of Psychology, ‡Department of Chemistry and Biomolecular Sciences, §Faculty of Human Sciences, and ⊥Department of Biomedical Sciences, Macquarie University , North Ryde, New South Wales 2109, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cornish
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000378:metabolism; D017397:Prefrontal Cortex / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002110:Caffeine
keywords: caffeine; cytoskeletal regulation; nanoflow LC−MS/MS/orbitofrontal cortex; neurological disease; proteomics/synaptic plasticity