Suppression of neuronal AMPKβ2 isoform impairs recognition memory and synaptic plasticity

AMP-activated protein kinase (AMPK) is an αβγ heterotrimer protein kinase that functions as a molecular sensor to maintain energy homeostasis. Accumulating evidence suggests a role of AMPK signaling in the regulation of synaptic plasticity and cognitive function; however, isoform-specific roles of A...

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Bibliographic Details
Published in:	Neurobiology of disease Vol. 201; p. 106664
Main Authors:	Swift, Nathaniel A., Yang, Qian, Jester, Hannah M., Zhou, Xueyan, Manuel, Adam, Kemp, Bruce E., Steinberg, Gregory R., Ma, Tao
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15-10-2024 Elsevier
Subjects:	AMPK Isoform LTP Memory Mouse model Synaptic plasticity AMPK Isoform LTP Mouse model Memory Synaptic plasticity
Online Access:	Get full text
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Summary:	AMP-activated protein kinase (AMPK) is an αβγ heterotrimer protein kinase that functions as a molecular sensor to maintain energy homeostasis. Accumulating evidence suggests a role of AMPK signaling in the regulation of synaptic plasticity and cognitive function; however, isoform-specific roles of AMPK in the central nervous system (CNS) remain elusive. Regulation of the AMPK activities has focused on the manipulation of the α or γ subunit. Meanwhile, accumulating evidence indicates that the β subunit is critical for sensing nutrients such as fatty acids and glycogen to control AMPK activity. Here, we generated transgenic mice with conditional suppression of either AMPKβ1 or β2 in neurons and characterized potential isoform-specific roles of AMPKβ in cognitive function and underlying mechanisms. We found that AMPKβ2 (but not β1) suppression resulted in impaired recognition memory, reduced hippocampal synaptic plasticity, and altered structure of hippocampal postsynaptic densities and dendritic spines. Our study implicates a role for the AMPKβ2 isoform in the regulation of synaptic and cognitive function. •Development of transgenic mice with neuronal suppression of AMPKβ isoforms.•Mice with AMPKβ1 suppression exhibit normal synaptic and cognitive function.•Suppression of AMPKβ2 leads to LTP failure and impaired recognition memory.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0969-9961 1095-953X 1095-953X
DOI:	10.1016/j.nbd.2024.106664