Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb;14(1):63-9.
doi: 10.1038/tpj.2013.6. Epub 2013 Mar 26.

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

M L Tan  1 , B A Dyck  1 , J Gabriele  1 , R P Daya  1 , N Thomas  1 , C Sookram  1 , D Basu  1 , M A Ferro  1 , V Z Chong  1 , R K Mishra  1
Affiliations

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

M L Tan et al. Pharmacogenomics J. 2014 Feb.

Abstract

Synapsins are neuronal phosphoproteins crucial to regulating the processes required for normal neurotransmitter release. Synapsin II, in particular, has been implied as a candidate gene for schizophrenia. This study investigated synapsin II mRNA expression, using real-time reverse transcriptase-PCR, in coded dorsolateral prefrontal cortical samples provided by the Stanley Foundation Neuropathology Consortium. Synapsin IIa was decreased in patients with schizophrenia when compared with both healthy subjects and patients with bipolar disorder, whereas synapsin IIb was only significantly reduced in patients with schizophrenia when compared with healthy subjects but not in patients with bipolar disorder. Furthermore, lifetime antipsychotic drug use was positively associated with synapsin IIa expression in patients with schizophrenia. Results suggest that impairment of synaptic transmission by synapsin II reduction may contribute to dysregulated convergent molecular mechanisms, which result in aberrant neural circuits that characterize schizophrenia, while implicating involvement of synapsin II in therapeutic mechanisms of currently prescribed antipsychotic drugs.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

All authors report neither competing financial interests nor potential conflicts of interest in relation to the work described.

Figures

Figure 1
Figure 1
Representative amplification plot of Real Time RT-PCR data for (A) synapsin IIa, (B) synapsin IIb, and (C) housekeeping gene cyclophilin in the dorsolateral prefrontal cortex of normal controls and patients with schizophrenia. Forward primer for synapsin IIa - 5′ ATCTGAAAAGAGGCTGGC 3′; reverse primer for synapsin IIa - 5′ GACTTGTTGAGCTGTGGG 3′. Forward primer for synapsin IIb - 5′ AGACCCCTAACAACCCAG 3′; reverse primer for synapsin IIb - 5′ CTTGTTTTGGCCCTACTG 3′. Forward and reverse primers for housekeeping cyclophilin: 5′ GCAAGACCAGCAAGAAGA 3′; and 5′ CAGCGAGAGCACAAAGAT 3′ respectively.
Figure 1
Figure 1
Representative amplification plot of Real Time RT-PCR data for (A) synapsin IIa, (B) synapsin IIb, and (C) housekeeping gene cyclophilin in the dorsolateral prefrontal cortex of normal controls and patients with schizophrenia. Forward primer for synapsin IIa - 5′ ATCTGAAAAGAGGCTGGC 3′; reverse primer for synapsin IIa - 5′ GACTTGTTGAGCTGTGGG 3′. Forward primer for synapsin IIb - 5′ AGACCCCTAACAACCCAG 3′; reverse primer for synapsin IIb - 5′ CTTGTTTTGGCCCTACTG 3′. Forward and reverse primers for housekeeping cyclophilin: 5′ GCAAGACCAGCAAGAAGA 3′; and 5′ CAGCGAGAGCACAAAGAT 3′ respectively.
Figure 1
Figure 1
Representative amplification plot of Real Time RT-PCR data for (A) synapsin IIa, (B) synapsin IIb, and (C) housekeeping gene cyclophilin in the dorsolateral prefrontal cortex of normal controls and patients with schizophrenia. Forward primer for synapsin IIa - 5′ ATCTGAAAAGAGGCTGGC 3′; reverse primer for synapsin IIa - 5′ GACTTGTTGAGCTGTGGG 3′. Forward primer for synapsin IIb - 5′ AGACCCCTAACAACCCAG 3′; reverse primer for synapsin IIb - 5′ CTTGTTTTGGCCCTACTG 3′. Forward and reverse primers for housekeeping cyclophilin: 5′ GCAAGACCAGCAAGAAGA 3′; and 5′ CAGCGAGAGCACAAAGAT 3′ respectively.
Figure 2
Figure 2
Representative amplification plot of Real Time RT-PCR data for (A) synapsin IIa, (B) synapsin IIb, and (C) housekeeping gene cyclophilin in the dorsolateral prefrontal cortex of normal controls and patients with bipolar disorder. Forward primer for synapsin IIa - 5′ ATCTGAAAAGAGGCTGGC 3′; reverse primer for synapsin IIa - 5′ GACTTGTTGAGCTGTGGG 3′. Forward primer for synapsin IIb - 5′ AGACCCCTAACAACCCAG 3′; reverse primer for synapsin IIb - 5′ CTTGTTTTGGCCCTACTG 3′. Forward and reverse primers for housekeeping cyclophilin: 5′ GCAAGACCAGCAAGAAGA 3′; and 5′ CAGCGAGAGCACAAAGAT 3′ respectively.
Figure 2
Figure 2
Representative amplification plot of Real Time RT-PCR data for (A) synapsin IIa, (B) synapsin IIb, and (C) housekeeping gene cyclophilin in the dorsolateral prefrontal cortex of normal controls and patients with bipolar disorder. Forward primer for synapsin IIa - 5′ ATCTGAAAAGAGGCTGGC 3′; reverse primer for synapsin IIa - 5′ GACTTGTTGAGCTGTGGG 3′. Forward primer for synapsin IIb - 5′ AGACCCCTAACAACCCAG 3′; reverse primer for synapsin IIb - 5′ CTTGTTTTGGCCCTACTG 3′. Forward and reverse primers for housekeeping cyclophilin: 5′ GCAAGACCAGCAAGAAGA 3′; and 5′ CAGCGAGAGCACAAAGAT 3′ respectively.
Figure 2
Figure 2
Representative amplification plot of Real Time RT-PCR data for (A) synapsin IIa, (B) synapsin IIb, and (C) housekeeping gene cyclophilin in the dorsolateral prefrontal cortex of normal controls and patients with bipolar disorder. Forward primer for synapsin IIa - 5′ ATCTGAAAAGAGGCTGGC 3′; reverse primer for synapsin IIa - 5′ GACTTGTTGAGCTGTGGG 3′. Forward primer for synapsin IIb - 5′ AGACCCCTAACAACCCAG 3′; reverse primer for synapsin IIb - 5′ CTTGTTTTGGCCCTACTG 3′. Forward and reverse primers for housekeeping cyclophilin: 5′ GCAAGACCAGCAAGAAGA 3′; and 5′ CAGCGAGAGCACAAAGAT 3′ respectively.
Figure 3
Figure 3
Synapsin IIa mRNA in post-mortem dorsolateral prefrontal cortex brain specimens. Real Time RT-PCR was performed on 105 specimens obtained from the SFNC. Synapsin IIa was significantly reduced in patients with schizophrenia (SCZ) (P<0.0001) compared to normal controls (CTL) and patients with bipolar disorder (BPD). Data are presented as box plots of log-transformed mean synapsin IIa mRNA expressions with shaded circles identifying outliers.
Figure 4
Figure 4
Synapsin IIb mRNA expression in post-mortem dorsolateral prefrontal cortex brain specimens. Real Time RT-PCR was performed on 105 specimens obtained from the SFNC. Synapsin IIb was significantly decreased in patients with schizophrenia (SCZ) compared to normal controls (CTL) (P<0.030). However, no significant differences were observed between patients with schizophrenia (SCZ) and bipolar disorder (BPD). Data are presented as box plots of log-transformed mean synapsin IIb mRNA expressions.
Figure 5
Figure 5
Graph depicting a direct linear relationship between expression levels of synapsin IIa mRNA (expressed as copy numbers) and lifetime antipsychotic drug use (expressed as fluphenazine equivalents) in patients with schizophrenia. A solid line represents a fitted regression line, a dotted line represents the probability (0.95) that the “true” fitted line (in the population) falls between the bands, while the shaded region depicts the 95% confidence interval.
Figure 6
Figure 6
Graph depicting a direct linear relationship between expression levels of synapsin IIb mRNA (expressed as copy numbers) and lifetime antipsychotic drug use (expressed as fluphenazine equivalents) in patients with schizophrenia. A solid line represents a fitted regression line, a dotted line represents the probability (0.95) that the “true” fitted line (in the population) falls between the bands, while the shaded region depicts the 95% confidence interval.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Dyck BA, Skoblenick KJ, Castellano JM, Ki K, Thomas N, Mishra RK. Behavioral abnormalities in synapsin II knockout mice implicate a causal factor in schizophrenia. Synapse. 2009;63(8):662–672. - PubMed
    1. Dyck BA, Mishra RK. Regulation of Synapsin II by Dopaminergic Mechanisms. Dopamine: Function, Regulation and Health Effects. New York: Nova Science Publishers; 2011.
    1. Dyck BA, Beyaert MG, Ferro MA, Mishra RK. Medial prefrontal cortical synapsin II knock-down induces behavioral abnormalities in the rat: Examining synapsin II in the pathophysiology of schizophrenia. Schizophr Res. 2011;130(1–3):250–259. - PubMed
    1. Kasai K, Iwanami A, Yamasue H, Kuroki N, Nakagome K, Fukuda M. Neuroanatomy and neurophysiology in schizophrenia. Neurosci Res. 2002;43(2):93–110. - PubMed
    1. Goldman-Rakic PS. Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci. 1994;6(4):348–357. - PubMed

Publication types

MeSH terms