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Akt activation ameliorates deficits in hippocampal-dependent memory and activity-dependent synaptic protein synthesis in an Alzheimer’s disease mouse model
Activating Akt improves memory and protein production at brain connections involved in memory in an Alzheimer's mouse model
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Abstract
Significant decreases in key signaling proteins were observed in the hippocampus of one-month-old APP/PS1 mice compared to wild-type mice.
- Akt/mTOR signaling pathways are essential for new protein synthesis and synaptic plasticity.
- Decreased levels of pAkt1, pGSK3β, pmTOR, pS6 ribosomal protein, and p4E-BP1 were found in presymptomatic APP/PS1 mice.
- Activity-dependent protein synthesis at the synapse was impaired in presymptomatic APP/PS1 mice and remained deficient in young adults.
- Downregulation of Akt1 in C57BL/6 mice hindered synaptic activity-dependent protein synthesis at dendrites but not in the soma.
- Administration of an Akt activator improved memory recall and synaptic protein synthesis in three-month-old APP/PS1 mice.
- Inhibition of Akt in C57BL/6 mice led to memory recall deficits, suggesting a link between Akt signaling and memory function.
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