THE EFFECTS OF SYNAPSIN II KNOCK-DOWN IN THE RAT MEDIAL PREFRONTAL CORTEX ON ATTENTION

Abstract

It has been estimated that approximately 300,000 Canadians are afflicted with schizophrenia (SCZ). Due to the severity of symptoms as well as critical age of onset, the quality of life among SCZ patients can be poor; thus, further therapeutic research is of great interest. In addition to the more-common rodent models of SCZ (amphetamine sensitization, PCP sensitization, etc.), our lab has proposed the medial prefrontal cortex (mPFC) synapsin-II knockdown (KD) model. Prior to this study, the cognitive effects of mPFC synapsin-II KD had yet to be reported. Using a 14-day continuous infusion of antisense (AS) deoxyoligonucleotides for synapsin-II to the mPFC, the results of the KD model have been recreated for further study. The 5-choice-serial-reaction-time-task was utilized to determine the effects of mPFC synapsin-II KD on attention and vigilance. In addition to reductions in both PPI (p<0.05) and social interaction (p<0.05), as well as hyper-locomotion (p<0.05); rats treated with synapsin II AS performed significantly worse on the 5-CSRTT than did control (mismatch/aCSF) animals. The AS animals were significantly less likely to make correct responses (p<0.001), and significantly more likely to commit omissions (p<0.0001) and perseverative responses (p<0.05) than were control animals. Additionally, an [18F]FDG tracer and PET/CT scans were used to determine differences in brain metabolism due to synapsin-II KD. Results revealed significant reductions in [18F]FDG among AS treated rats (p<0.05) when compared to control animals. This reduction appeared to be a global result, however it followed 13-days of treatment which may account for the widespread effect. The mPFC synapsin-II KD model of SCZ has showcased cognitive and metabolic effects similar to that of SCZ. These findings, in conjunction with past research, provide evidence for the synapsin-II KD model as a viable rodent model of SCZ. Further research utilizing this model will provide valuable insight into the pathogenesis of SCZ and potential therapeutics.