Behavioral abnormalities in synapsin II knockout mice implicate a causal factor in schizophrenia.
Recent studies on the phosphoprotein synapsin II have revealed reduced expression in postmortem medial prefrontal cortex tissues from subjects with schizophrenia, and chronic antipsychotic drug treatment has resulted in concurrent increases in synapsin II mRNA and protein levels. Collectively, this research suggests a role of synapsin II in the pathophysiology of schizophrenia; however, whether synapsin II plays a causal role in this disease process still remains unclear. Therefore, the goal of this investigation was to examine whether synapsin II knockout mice display behavioral abnormalities commonly expressed in preclinical animal models of schizophrenia, namely deficits in prepulse inhibition (PPI), decreased social behavior, and locomotor hyperactivity. Results indicate that mice with knockout of the synapsin II gene demonstrate deficits in PPI at three prepulse intensities (67, 70, and 73 dB), along with deficits in habituation to startle to a 110 dB acoustic pulse. Knockout animals also expressed decreased social behavior and increased locomotor activity when compared to wildtype and heterozygous populations. Complete knockout of the synapsin II gene was confirmed in postmortem brain tissues via immunoblotting. In conclusion, these results confirm that synapsin II knockout mice display behavioral endophenotypes similar to established preclinical animal models of schizophrenia, and lend support to the notion that abnormalities in synapsin II expression may play a causal role in the underlying pathophysiological mechanisms of schizophrenia.
Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Bailee A
BA
Dyck
Kevin J
KJ
Skoblenick
Jessica M
JM
Castellano
Kitty
K
Ki
Nancy
N
Thomas
Ram K
RK
Mishra
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D006185:Habituation, Psychophysiologic / Q000235:genetics; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009433:Neural Inhibition / Q000235:genetics; D011571:Psychoacoustics; D013216:Reflex, Startle / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D016704:Synapsins / Q000172:deficiency* / Q000378:metabolism
D016704:Synapsins