Item Details

title

EFFECTS OF ISOFORM-SPECIFIC AMPKβ SUPPRESSION ON LEARNING & MEMORY IN MICE

author

Swift, Nathaniel Allender

abstract

AMP-activated protein kinase (AMPK) is a regulator of protein metabolism and energy homeostasis throughout the body comprising α, β, and γ subunits. Its catalytic α subunit has been implicated in learning & memory and is dysregulated in Alzheimer disease; however, little research has been conducted on the role of the regulatory β subunit on such processes. Here, we explored isoform-specific suppression of AMPKβ, primarily in the form of a heterozygous knockdown (β1 KD, β2 KD) and the effect of that suppression on learning & memory and related processes. We examined learning & memory through a battery of behavioral tests, hippocampal long-term potentiation (LTP) via electrophysiology, and postsynaptic CA1 dendritic structure via transmission electron microscopy, Golgi-Cox staining, and western blotting. Additionally, we assessed the phosphorylation of various AMPK-related proteins involved in de novo protein synthesis, a process integral to LTP and regulated by AMPK. We found that the suppression of AMPKβ2, not β1, resulted in impaired recognition memory and hippocampal LTP, which was supported by a decrease in postsynaptic density area and dendritic spine maturity in β2 KD mice. These data suggest that AMPKβ2 is vital to the maintenance of proper postsynaptic morphology, hippocampal LTP, and learning & memory.

subject

AMPK

dendritic spine

learning & memory

long-term potentiation

postsynaptic density

protein translation

contributor

Ma, Tao (advisor)

Raab-Graham, Kimberly F (committee member)

Jadiya, Pooja (committee member)

date

2023-07-25T17:48:39Z (accessioned)

2023 (issued)

degree

Neuroscience – MS (discipline)

embargo

2028-05-13 (terms)

2028-05-13 (liftdate)

identifier

http://hdl.handle.net/10339/102257 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis