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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    857—Prefrontal and Striatal Systems: Molecular Mechanisms

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    857.04: Extended exposure to sucrose results in persistent hyperactivity and changes to the proteome of the orbital frontal cortex in Sprague Dawley rats

    Location: Halls B-H

    *J. L. FRANKLIN1, M. MIRZAEI2, M. K. SAUER3, T. A. WEARNE3, J. HOMEWOOD3, A. K. GOODCHILD2, P. A. HAYNES4, J. L. CORNISH3;
    2Australian Sch. of Advanced Med., 3Psychology, 4Chem. and Biomolecular Sci., 1Macquarie Univ., Sydney, Australia

    Abstract Body: The consumption of sugar-sweetened soft drinks is increasing in our society. For many adults these drinks represent a substantial proportion of the total daily calories consumed. There is a large body of research that has examined how high sucrose diets might effect cardiovascular health, obesity and the development of diabetes, however far less is known about the consequences for mental health and neural function. Here we explored whether extended exposure to sucrose would alter locomotor behaviour. In addition to behavioral changes, the effect of chronic treatment with sucrose on protein expression in the orbitofrontal cortex (OFC) was examined. The OFC plays a critical role in decision making processes and as a secondary taste processing center, it also plays a critical role in taste reward associative learning. Dysfunction of the OFC has also been implicated in a number of neuropsychiatric conditions and has been linked to obesity and addiction behaviours. Method: Adult male Sprague Dawley (SD) rats, (n=12 per group), were treated for 26 days with either water or a 10 % sucrose solution. Body weight, chow and fluid consumption of the rats were measured daily. Locomotor behaviour was tested on the first and last day of treatment, then one week after treatment had ceased. Following final behavioural testing, brains were rapidly removed, snap frozen in liquid nitrogen then stored at -80°C until proteomic analysis of the OFC was conducted. Results: There were no between group differences in weight, however animals with free access to sucrose drank more fluid and ate less chow than control animals, p<0.001, sucrose consumption also escalated over time. During treatment there were no differences in locomotor activity, although when tested 7 days after chronic treatment (sucrose-free), the sucrose rats were significantly more active than control treated rats, p<0.05. Label free quantitative shotgun proteomic analyses identified a total of 1363 proteins in the OFC. Of these 185 proteins were upregulated and 100 proteins were down regulated in sucrose rats when compared to control. The top molecular functions related to these differentially expressed proteins were carbohydrate metabolism, DNA replication recombination and repair, small molecular biochemistry and protein synthesis. Conclusion: Extended sucrose consumption in rats had an enduring effect on locomotor activity when sucrose-free and differentially altered a wide range of proteins compared to control treated animals. Major proteomic effects were seen in proteins that relate to energy metabolism and the cellular response to stress

    Lay Language Summary: Our research suggests the long-term consumption of sugar-sweetened drinks in place of water can cause long lasting changes to behavior and a profound change in the chemistry of the brain.
    In most Westernised societies there has been an alarming increase in the consumption of sugar-sweetened drinks. For many adults these drinks represent a substantial proportion of their total daily caloric intake. This trend is not only contributing to the rising obesity epidemic, but may also produce changes in our behavior and brain chemistry. We anticipated that long-term exposure to drinking sucrose in rats would alter motor behavior and the chemical function of a key decision making area of the brain. We have been able to show that chronic sucrose consumption produces hyperactivity and changes to chemical proteins in the brain that relate to energy metabolism and stress of brain cells.
    Appropriate protein production is critical to both the structure and function of the brain. We have discovered that approximately 20% of the proteins in sugar-drinking rats were changed when compared to control rats. Of the 1363 proteins identified in the brain tissue examined, 185 proteins were increased, and 100 decreased in the sugar-drinking rats compared to control treated animals.
    These proteins have the potential to effect many different aspects of cell function in the brain. These include cellular lifespan, energy metabolism, cell-to-cell communication and DNA repair. Similar changes in proteins have also been seen in some cancers, in hypertension and metabolic disorders, and neurological disorders such as Alzheimer’s disease, Parkinson’s disease and schizophrenia. Further experimental research is now required to determine the specific mental health consequences of these sugar-induced changes in brain proteins.
    To carry out this research we provided rats with either water or a 10% sucrose solution to drink for 26 days. We tested motor activity on the first and last day of treatment, then again after 7 sucrose free days. Whilst on sucrose there were no differences in body weight or behavior between the two treatment groups, however one week following treatment, we found that the sucrose rats were hyperactive when compared to their water treated counterparts. We used mass spectrometry to detect and measure protein levels in the orbital frontal cortex of the forebrain. This part of the brain plays a critical role motor activity, taste learning, impulsivity and other decision-making processes. Dysfunction of this brain area has been implicated in a number of neuropsychiatric conditions, including addiction related behaviors and obesity.
    There is a large body of research that has examined the implications of a high sucrose diet for cardiovascular health, obesity and the development of diabetes, however far less is known about the consequences for mental health and the function of brain cells. This study indicates that a high sucrose diet can significantly change brain chemistry and behavior.
    We are currently extending this research to investigate the effect of long-term sucrose consumption in an adolescent rat population and on more complex behaviours. The current study provides evidence that a high sucrose diet has consequences beyond our physical health; it can also alter behavior and the way our brain works.