English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The group II metabotropic glutamate 2/3 (mGlu 2/3 ) receptor antagonist LY341495 produces antidepressant-like effects by acting on mammalian target of rapamycin complex 1 (mTORC1) signaling and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in rodent. We investigated whether LY341495 affects neuroplasticity via these mechanisms in rat primary hippocampal cultures under conditions of dexamethasone (DEX)-induced neurotoxicity. Ketamine was used for comparison. Hippocampal cultures were treated with LY341495 under conditions of DEX-induced toxicity. Changes in mTORC1-mediated proteins were determined by Western blotting analyses. Changes in dendritic outgrowth and spine density were evaluated via immunostaining. LY341495 significantly prevented DEX-induced decreases in the levels of mTORC1, 4E-BP1, and p70S6K phosphorylation as well as the levels of the synaptic proteins. These effects were blocked by pretreatment with the AMPA receptor inhibitor 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo(f)quinoxaline (NBQX) and the mTORC1 inhibitor rapamycin. LY341495 significantly attenuated DEX-induced decreases in dendritic outgrowth and spine density. Pretreatment with rapamycin and NBQX blocked these effects of LY341495. Further analyses indicted that induction of BDNF expression produced by LY341495 was blocked by pretreatment with NBQX and rapamycin. LY341495 has neuroplastic effects by acting on AMPA receptor-mTORC1 signaling under neurotoxic conditions. Therefore, activation of AMPA receptor and mTORC1 signaling, which enhance neuroplasticity, may be novel targets for new antidepressants.

AMPA receptor-mTORC1 signaling activation is required for neuroplastic effects of LY341495 in rat hippocampal neurons