Medial prefrontal cortical synapsin II knock-down induces behavioral abnormalities in the rat: Examining synapsin II in the pathophysiology of schizophrenia

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

“…In another study, a decrease in SynII gene expression in postmortem brain tissue of BPD patients might be explained by the presence of hypomethylated I CpG islands found in this gene [32]. The findings in humans are, in part, reproducible in animal models because a Syn II knock-out (KO) animal model results in a schizophrenic-like phenotype [28–30]. The third member of the family, synapsin 3, has also been implicated in SCZ because a decrease in its expression was observed in the prefrontal cortex of individuals with SCZ [33].…”

Synapsin II gene expression in the dorsolateral prefrontal cortex of brain specimens from patients with schizophrenia and bipolar disorder: effect of lifetime intake of antipsychotic drugs

“…Synapsins are a family of neuronal phosphoproteins that are important for neurotransmitter release, synaptogenesis and the maintenance of synaptic vesicular pools (1–3). There is an increasing body of evidence to support a role for aberrant synaptic processes in the underlying pathophysiology of schizophrenia (2;4–8).…”

“…Our cDNA study revealed that haloperidol, a typical antipsychotic drug and an antagonist of the inhibitory dopamine D2 receptor, increases mRNA expression of synapsin II in the rat striatum (11;18;19). Treatment with the atypical antipsychotic drug olanzapine, on the other hand, increases synapsin II expression in the medial prefrontal cortex (mPFC) of synapsin II knock-down rats (3). Furthermore, treatment with SCH23390, an antagonist of the excitatory dopamine D1 receptor, reduces concentrations of synapsin II, whereas treatment with SKF38393, an agonist of the dopamine D1 receptor, up-regulates expression of synapsin II in primary cell cultures (18).…”

“…In addition to synaptic proteins however, vesicular transporters are also present on synaptic vesicles for the uptake and storage of their respective neurotransmitters into the synaptic vesicles for subsequent release into the synaptic cleft (8;28). Evidence from previous studies have shown that synapsin II reduction in the prefrontal cortex is accompanied by reductions in VGAT (GABA vesicular transporter), VGLUT1 and VGLUT2 (vesicular glutamate transporters) (3). Altered prefrontal glutamatergic signaling, as a result of subnormal synapsin II expression, can subsequently disrupt local and long loop pathways and influence the release of neurotransmitters, including GABA and dopamine, in both the cortical and subcortical regions (2;3;29).…”

Change in expression of vesicular protein synapsin II by chronic treatment with D2 allosteric modulator PAOPA

“…The lifetime antipsychotic drug use in these studies has been shown to positively correlate with synapsin II expression, particular the synapsin IIa isoform, via interaction with dopamine D1 and D2 receptors (D2R) [10,26,41,47]. Finally, previous studies from our lab have also shown that knockdown of synapsin II globally [17,18] as well as specifically within the medial prefrontal cortical regions of animal models [16,19], induces schizophrenia-like behavioral abnormalities. Taken together, this evidence supports a significant role of the synapsin II protein within the etiology of schizophrenia.…”