THE SUCROSE INTAKE CHANGES STRESS-INDUCED BEHAVIOR VIA GLUCOSE METABOLISM AND NORADRENERGIC NEURONAL SYSTEM

Abstract Background 322 million people globally are suffering from major depressive disorder (MDD). MDD is projected to become the primary cause of disease burden by 2030. Lifestyle habits have attracted attention as potential environmental factors for MDD. However, it remains unclear how lifestyle habits affect pathophysiology of depression. Aims & Objectives In this study, we analyzed lifestyle habits in high-risk subjects of major depressive disorder (HRMDD) by using the clinical database from Resource Center for Health Science (RECHS). A notable observation from our analysis revealed that sucrose intake was elevated among HRMDD subjects. Method To investigate whether sucrose intake affects stress-induced depression-like behaviors, we observed the behaviors of mice took freely sucrose via water bottle under the chronic unpredictable mild stress (CUMS). Results Our findings revealed that sucrose intake attenuated CUMS-induced hyperactivity and aggressive behavior but not social deficit. Unexpectedly, the sucrose intake under CUMS impaired recognition memory. Furthermore, sucrose intake under stress increased serum corticosterone levels and blood glucose levels. In association with high blood glucose level, CUMS changed expression of mRNA related to glucose and lactate metabolism such as glucose transporter, lactate dehydrogenase, and monocarboxylate transporter in the prefrontal cortex (PFC). Further, CUMS reduced noradrenaline (NA) levels in the PFC. Sucrose intake under CUMS ameliorated reduction in NA levels, although it decreased the turnover of NA, which associated with expression of decrease in adrenergic α1 receptors, but of an increase in of adrenergic α2 receptors. Antidepressants targeting noradrenergic neuronal system alleviated these depression-like behaviors and cognitive dysfunction. Discussion & Conclusion In conclusion, our data suggest that high sucrose intake in HRMDD may cope stress-induced aggression and hyperactivity. However, this comes with the unintended consequence of impairment of cognition. These contradictory findings may be associated with changes of glucose and lactate metabolism and noradrenergic system in the PFC.