論文

国際誌
2021年2月1日

RAGE signaling is required for AMPA receptor dysfunction in the hippocampus of hyperglycemic mice.

Physiology & behavior
  • Zeinab Momeni
  • ,
  • Maricris Bautista
  • ,
  • Joseph Neapetung
  • ,
  • Rylan Urban
  • ,
  • Yasuhiko Yamamoto
  • ,
  • Anand Krishnan
  • ,
  • Verónica A Campanucci

229
開始ページ
113255
終了ページ
113255
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.physbeh.2020.113255

Diabetes in humans has been associated for a long time with cognitive dysfunction. In rodent animal models, cognitive dysfunction can manifest as impaired hippocampal synaptic plasticity. Particular attention has been concentrated on the receptor for advanced glycation end products (RAGE), which is implicated in multiple diabetic complications involving the development of vascular and peripheral nerve abnormalities. In this study, we hypothesize that RAGE signaling alters glutamate receptor function and expression, impairing synaptic transmission in the hippocampus. Using preparations of hippocampal slices from male mice, we show a RAGE-dependent decrease in long-term potentiation (LTP) and an increase in paired-pulse facilitation (PPF) following streptozotocin (STZ)-induced diabetes. Consistently, in hippocampal cultures from male and female neonatal mice, high glucose caused a RAGE-dependent reduction of AMPA- but not NMDA-evoked currents, and an increase in cytosolic reactive oxygen species (ROS). Consistently, when cultures were co-treated with high glucose and the RAGE antagonist FPS-ZM1, AMPA-evoked currents were unchanged. Hippocampi from STZ-induced hyperglycemic wild type (WT) mice showed increased RAGE expression concomitant with a decrease of both expression and phosphorylation (Ser 831 and 845) of the AMPA GluA1 subunit. We found these changes correlated to activation of the MAPK pathway, consistent with decreased pJNK/JNK ratio and the JNK kinase, pMEK7. As no changes in expression or phosphorylation of regulatory proteins were observed in hippocampi from STZ-induced hyperglycemic RAGE-KO mice, we report a RAGE-dependent impairment in the hippocampi of hyperglycemic WT mice, with reduced AMPA receptor expression/function and LTP deficits.

リンク情報
DOI
https://doi.org/10.1016/j.physbeh.2020.113255
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33221393
ID情報
  • DOI : 10.1016/j.physbeh.2020.113255
  • PubMed ID : 33221393

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