8TH SRCA SYMPOSIUM ON THE CEREBELLUM: FROM DEVELOPMENT TO DISEASE

Abstract

Increasing lines of evidence indicate that cerebellum is involved in the cognition and pathophysiology of psychiatric disorders such as depression. It has been well-evident that experiencing early life adversities is able to negatively affect the brain and behavior in later life through a variety of mechanisms including mitochondrial dysfunction. Abnormal mitochondrial function is associated with impairment in energy hemostasis, massive production of reactive oxygen species, initiation of immune-inflammatory and apoptotic pathways, and consequently brain damage and dysfunction. Applying maternal separation stress (MS) to male rats on postnatal day (PND) 2-14, we showed that MS is able to induce depressive-like behaviors (using forced swimming test, sucrose preference test and splash test) and cerebellar mitochondrial dysfunction (Increased ROS production, Decreased ATP and GSH) in adult male rats (PND 60). We also showed that treating animals with chronic fluoxetine (5 mg/kg/day, i.p), selegiline (1 mg/kg/day, i.p) and voluntary running wheel exercise during adolescence (PND 30 to PND 60) effectively attenuated the behavioral deficits and cerebellar mitochondrial dysfunction in adult male rats. These results suggest that cerebellar mitochondrial dysfunction at least partly is involved in the pathophysiology of psychiatric disorders such as depression. Also, we highlighted the importance of adolescence as a period in which treating subjects with (non) pharmacological therapies is able to mitigate the negative effects of early life stress on brain and behavior in adulthood.