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Nobiletin improves emotional and novelty recognition memory but not spatial referential memory

Abstract

How to maintain and enhance cognitive functions for both aged and young populations is a highly interesting subject. But candidate memory-enhancing reagents are tested almost exclusively on lesioned or aged animals. Also, there is insufficient information on the type of memory these reagents can improve. Working memory, located in the prefrontal cortex, manages short-term sensory information, but, by gaining significant relevance, this information is converted to long-term memory by hippocampal formation and/or amygdala, followed by tagging with space–time or emotional cues, respectively. Nobiletin is a product of citrus peel known for cognitive-enhancing effects in various pharmacological and neurodegenerative disease models, yet, it is not well studied in non-lesioned animals and the type of memory that nobiletin can improve remains unclear. In this study, 8-week-old male mice were tested using behavioral measurements for working, spatial referential, emotional and visual recognition memory after daily administration of nobiletin. While nobiletin did not induce any change of spontaneous activity in the open field test, freezing by fear conditioning and novel object recognition increased. However, the effectiveness of spatial navigation in the Y-maze and Morris water maze was not improved. These results mean that nobiletin can specifically improve memories of emotionally salient information associated with fear and novelty, but not of spatial information without emotional saliency. Accordingly, the use of nobiletin on normal subjects as a memory enhancer would be more effective on emotional types but may have limited value for the improvement of episodic memories.

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Abbreviations

PKA:

Protein kinase A

ERK:

Extracellular signal-regulated kinase

CREB:

Cyclic-AMP-responsive-element-binding protein

LTP:

Long-term potentiation

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Aβ:

Amyloid-beta

NMDA:

N-Methyl-d-aspartate

ANOVA:

Analysis of variation

Tukey’s HSD:

Tukey’s honest significant difference

SEM:

Standard error of the mean

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Acknowledgements

The authors have no conflicts of interest to disclose. Financial support and preparation of the article was provided by the corresponding author. The research was conduct mainly by the first two authors. Other co-authors contributed to study design, data analysis and interpretation. No funding sources were involved.

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Correspondence to Sungho Maeng.

Additional information

J. Kang and J.-W. Shin contributed equally to this work.

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Kang, J., Shin, JW., Kim, Yr. et al. Nobiletin improves emotional and novelty recognition memory but not spatial referential memory. J Nat Med 71, 181–189 (2017). https://doi.org/10.1007/s11418-016-1047-4

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Keywords

  • Nobiletin
  • Donepezil
  • Working memory
  • Contextual memory
  • Emotional memory
  • Visual recognition memory