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Pseudomonas aeruginosa‐ induced pulmonary endothelial amyloid proteins impair long‐term plasticity
Author(s) -
Lin Mike T,
Balczon Ron,
Morrow K. Adam,
Wagener Brant M,
Pittet JeanFrancois,
Stevens Troy
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.861.3
Subject(s) - long term potentiation , cytotoxicity , synaptic plasticity , chemistry , amyloid (mycology) , hippocampal formation , cytotoxic t cell , microbiology and biotechnology , biology , neuroscience , biochemistry , in vitro , inorganic chemistry , receptor
We have recently reported that following bacterial infection with Pseudomonas aeruginosa , injury to the pulmonary endothelium induces tau hyperphosphorylation and release as a cytotoxic amyloid protein. Further, cytotoxic amyloid production requires an intact type 3 secretion system (PA103 strain), because a non‐functional type 3 secretion system (e.g. ΔPcrV strain) does not result in the production of cytotoxic amyloid oligomers. Aberrant formation of protein aggregation is a common mechanism linked to several neurodegenerative diseases. Therefore, in this study we tested whether endothelial amyloid protein(s) affect synaptic plasticity. We employed the well‐characterized hippocampal Schaffer Collateral‐CA1 synaptic pathway to study the effect of supernatants from PA103‐, ΔPcrV‐, or non‐treated endothelial cells on long‐term potentiation (LTP) as a cellular model for animal learning. In field recordings, high frequency stimulation induced LTP. In mouse hippocampal slices exposed to supernatants from ΔPcrV‐ or non‐infected endothelial cells, the induced LTP were 192 ± 12% (n = 6) and 180 ± 16% (n = 6), respectively. In comparison, in slices exposed to supernatant from PA103‐infected endothelial cells, the LTP was reduced (128 ± 9.0%, n = 9; P < 0.05, ANOVA). Importantly, LTP suppression seemed to be ameliorated when endothelial amyloid(s) were immunodepleted with a pan antibody that recognizes neural amyloids, A11 (LTP: 176 ± 18%, n = 4). These results suggest that A11 neutralizes PA103‐induced amyloid cytotoxicity. Whole cell patch clamp recordings in CA1 pyramidal neurons further showed that hyperexcitability and changes in presynaptic neurotransmitter release might be attributable to the LTP suppression induced by endothelial amyloid cytotoxicity. Taken together, our results suggest that acute pneumonia may directly or indirectly impair brain cognitive function. Support or Funding Information Supported by HL66299 and HL60224 (TS) and AHA16POST27250139 (KAM).