Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice

Neural Plasticity
Hua YangJian Fei

Abstract

Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, c...Continue Reading

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Citations

Oct 6, 2018·The American Journal of Chinese Medicine·Wei XiongHua Su
Jul 31, 2019·Brain and Behavior·Zhong-Guang SunWei Wu
Sep 5, 2019·International Journal of Molecular Sciences·Vesna LazarevicPer Svenningsson
Jun 20, 2020·Acta Biochimica Et Biophysica Sinica·Ming MaJian Fei
Feb 2, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Feng ChenYan Wang
Apr 4, 2021·Brain Sciences·Cong LiuDesheng Liang

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Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

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Startle Reflex

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