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

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.