Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice

Kelly Dineley, Dale Hogan, Wen Ru Zhang, Giulio Taglialatela

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Misfolded amyloid beta peptide (Aβ) is a pathological hallmark of Alzheimer's disease (AD), a neurodegenerative illness characterized by cognitive deficits and neuronal loss. Transgenic mouse models of Aβ over-production indicate that Aβ-induced cognitive deficits occur in the absence of overt neuronal death, suggesting that while extensive neuronal death may be associated with later stages of the human disease, subtle physiological changes may underlie initial cognitive deficits. Therefore, identifying signaling elements involved in those Aβ-induced cognitive impairments that occur prior to loss of neurons may reveal new potential pharmacological targets. Here, we report that the enzymatic activity of calcineurin, a key protein phosphatase involved in phosphorylation-dependent kinase activity crucial for synaptic plasticity and memory function, is upregulated in the CNS of the Tg2576 animal model for Aβ over-production. Furthermore, acute treatment of Tg2576 mice with the calcineurin inhibitor FK506 (10 mg/kg i.p.) improves memory function. These results indicate that calcineurin may mediate some of the cognitive effects of excess Aβ such that inhibition of calcineurin shall be further explored as a potential treatment to reverse cognitive impairments in AD.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalNeurobiology of Learning and Memory
Volume88
Issue number2
DOIs
StatePublished - Sep 2007

Fingerprint

Calcineurin
Transgenic Mice
Learning
Alzheimer Disease
Neuronal Plasticity
Phosphoprotein Phosphatases
Amyloid beta-Peptides
Tacrolimus
Phosphotransferases
Animal Models
Phosphorylation
Pharmacology
Neurons
Inhibition (Psychology)
Cognitive Dysfunction

Keywords

  • Amyloid beta
  • Behavior
  • Calcineurin
  • Fear conditioning
  • FK506
  • SY5Y cells
  • Tg2576 mice

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Experimental and Cognitive Psychology

Cite this

Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice. / Dineley, Kelly; Hogan, Dale; Zhang, Wen Ru; Taglialatela, Giulio.

In: Neurobiology of Learning and Memory, Vol. 88, No. 2, 09.2007, p. 217-224.

Research output: Contribution to journalArticle

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