The ketamine metabolite (2R,6R)‐hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer's disease

Jun 27, 2024Alzheimer's & dementia : the journal of the Alzheimer's Association

(2R,6R)-hydroxynorketamine, a ketamine breakdown product, restores protein production, brain cell connections, and memory in mouse models of Alzheimer's disease

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Abstract

HNK treatment may improve memory and synaptic function in Alzheimer's disease models.

  • HNK activates important signaling pathways (ERK, mTOR, S6) in the hippocampus.
  • In amyloid-β oligomer-infused mice, HNK rescues memory and synaptic function through ERK1/2 signaling.
  • HNK also corrects transcription issues and memory deficits in aged APP/PS1 mice.
  • These findings suggest that HNK could be a potential treatment for Alzheimer's disease.

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Key numbers

20%
Decrease in Protein Synthesis
Reduction in protein synthesis observed in hippocampal slices treated with .
0.5 mg/kg
Memory Deficits Reversed in
Dosing of administered to for memory recovery.

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