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AAV-Mediated Overexpression of Neuroserpin in the Hippocampus Decreases PSD-95 Expression but Does Not Affect Hippocampal-Dependent Learning and Memory

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  • Vicky W K Tsang
  • Deborah Young
  • Matthew J During
  • Nigel P Birch

Abstract

Neuroserpin is a serine protease inhibitor, or serpin, that is expressed in the nervous system and inhibits the protease tissue plasminogen activator (tPA). Neuroserpin has been suggested to play a role in learning and memory but direct evidence for such a role is lacking. Here we have used an adeno-associated virus (AAV) vector expression system to investigate the effect of neuroserpin on hippocampal-dependent learning and memory in the young adult rat. A FLAG-tagged neuroserpin construct was initially characterized by in vitro transcription/translation and transfection into HEK293 cells and shown to interact with tPA and be targeted to the secretory pathway. Targeted injection of a chimeric AAV1/2 vector expressing FLAG-neuroserpin resulted in localized overexpression in the dorsal hippocampus. Neuroserpin overexpression led to the appearance of an unstable neuroserpin:tPA complex in zymographic assays consistent with interaction with endogenous tPA in vivo. Rats overexpressing neuroserpin also showed a significant decrease in the levels of postsynaptic density protein 95, a major postsynaptic scaffolding protein. Three weeks after injection, a range of behavioural tests was performed to measure spatial and associative learning and memory, as well as innate and acquired fear. These tests provided no evidence of a role for neuroserpin in hippocampal-dependent learning and memory. In summary this study does not support a role for neuroserpin in hippocampal-dependent learning and memory in young adult rats but does suggest an involvement of neuroserpin in hippocampal synaptic plasticity.

Suggested Citation

  • Vicky W K Tsang & Deborah Young & Matthew J During & Nigel P Birch, 2014. "AAV-Mediated Overexpression of Neuroserpin in the Hippocampus Decreases PSD-95 Expression but Does Not Affect Hippocampal-Dependent Learning and Memory," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-12, March.
    • Handle: RePEc:plo:pone00:0091050
    DOI: 10.1371/journal.pone.0091050
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    References listed on IDEAS

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    1. Kay M. Tye & Rohit Prakash & Sung-Yon Kim & Lief E. Fenno & Logan Grosenick & Hosniya Zarabi & Kimberly R. Thompson & Viviana Gradinaru & Charu Ramakrishnan & Karl Deisseroth, 2011. "Amygdala circuitry mediating reversible and bidirectional control of anxiety," Nature, Nature, vol. 471(7338), pages 358-362, March.
    2. Dong V Wang & Fang Wang & Jun Liu & Lu Zhang & Zhiru Wang & Longnian Lin, 2011. "Neurons in the Amygdala with Response-Selectivity for Anxiety in Two Ethologically Based Tests," PLOS ONE, Public Library of Science, vol. 6(4), pages 1-7, April.
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