The ketamine metabolite (2R,6R)-hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer's disease.
Felipe C RibeiroDanielle CozachencoElentina K ArgyrousiAgnieszka StaniszewskiShane WiebeJoao D CalixtroRubens Soares-NetoAycheh Al-ChamiFatema El SayeghSara BermudezEmily ArsenaultMarcelo CossenzaJean-Claude LacailleKarim NaderHongyu SunFernanda G De FeliceMychael V LourencoOttavio ArancioArgel Aguilar-VallesNahum SonenbergSergio T FerreiraPublished in: Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
The ketamine metabolite HNK activates hippocampal ERK/mTOR/S6 signaling pathways. HNK corrects hippocampal synaptic and memory defects in two mouse models of AD. Rescue of synaptic and memory impairments by HNK depends on ERK signaling. HNK corrects aberrant transcriptional signatures in APP/PS1 mice.
Keyphrases
- mouse model
- signaling pathway
- working memory
- pi k akt
- cell proliferation
- cerebral ischemia
- temporal lobe epilepsy
- pain management
- prefrontal cortex
- gene expression
- transcription factor
- epithelial mesenchymal transition
- high fat diet induced
- genome wide
- type diabetes
- blood brain barrier
- dna methylation
- chronic pain
- insulin resistance
- heat shock
- subarachnoid hemorrhage
- wild type
- heat stress