Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers

Shaomin Li, Ming Jin, Dainan Zhang, Ting Yang, Thomas Koeglsperger, Hongjun Fu, Dennis J. Selkoe

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

A central question about human brain aging is whether cognitive enrichment slows the development of Alzheimer changes. Here, we show that prolonged exposure to an enriched environment (EE) facilitated signaling in the hippocampus of wildtype mice that promoted long-term potentiation. A key feature of the EE effect was activation of β2-adrenergic receptors and downstream cAMP/ PKA signaling. This EE pathway prevented LTP inhibition by soluble oligomers of amyloid b-protein (Aβ) isolated from AD cortex. Protection by EE occurred in both young and middle-aged wild-type mice. Exposure to novelty afforded greater protection than did aerobic exercise. Mice chronically fed a β-adrenergic agonist without EE were protected from hippocampal impairment by Aβ oligomers. Thus, EE enhances hippocampal synaptic plasticity by activating β-adrenoceptor signaling and mitigating synaptotoxicity of human Aβ oligomers. These mechanistic insights support using prolonged exposure to cognitive novelty and/or oral b-adrenergic agonists to lessen the effects of Aβ accumulation during aging

Original languageEnglish (US)
Pages (from-to)929-941
Number of pages13
JournalNeuron
Volume77
Issue number5
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Adrenergic Agents
Adrenergic Agonists
Adrenergic Receptors
Serum Amyloid A Protein
Neuronal Plasticity
Long-Term Potentiation
Hippocampus
Exercise
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers. / Li, Shaomin; Jin, Ming; Zhang, Dainan; Yang, Ting; Koeglsperger, Thomas; Fu, Hongjun; Selkoe, Dennis J.

In: Neuron, Vol. 77, No. 5, 01.01.2013, p. 929-941.

Research output: Contribution to journalArticle

Li, Shaomin ; Jin, Ming ; Zhang, Dainan ; Yang, Ting ; Koeglsperger, Thomas ; Fu, Hongjun ; Selkoe, Dennis J. / Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers. In: Neuron. 2013 ; Vol. 77, No. 5. pp. 929-941.
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