Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice

Aomine, Yoshiatsu; Shimo, Yuto; Sakurai, Koki; Abe, Mayuka; Macpherson, Tom; Ozawa, Takaaki; Hikida, Takatoshi

doi:https://doi.org/10.1111/jnc.16227

Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice

Aomine, Yoshiatsu; Shimo, Yuto; Sakurai, Koki et al.

Journal of Neurochemistry, 2024, 169(1), e16227

Number of Access:212（2025-06-13 10:30 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98306

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Title	Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice
Creator	ORCID 0009-0005-1569-8207 0009-0005-1569-8207 CreatorName Aomine, Yoshiatsu
	CreatorName Shimo, Yuto
	researchmap permalink kokisakurai kokisakurai CreatorName Sakurai, Koki
	CreatorName Abe, Mayuka
	NRID 1000040821898 1000040821898 researchmap permalink macpherson macpherson Scopus Author ID 55330509300 55330509300 CreatorName Macpherson, Tom
	NRID 1000090625352 1000090625352 ORCID 0000-0003-3633-7062 0000-0003-3633-7062 researchmap permalink takaaki_ozawa takaaki_ozawa Scopus Author ID 56312563400 56312563400 CreatorName Ozawa, Takaaki
	NRID 1000070421378 1000070421378 ORCID 0000-0002-8653-311X 0000-0002-8653-311X researchmap permalink hikida hikida Scopus Author ID 7006504625 7006504625 CreatorName Hikida, Takatoshi
Subject	cognitive flexibility
	protein–protein interaction network
	reversal learning
	RNA-seq
	transcription factor analysis
	visual discrimination learning
Description	Aomine Y., Shimo Y., Sakurai K., et al. Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice. Journal of Neurochemistry, (2024); https://doi.org/10.1111/jnc.16227.
Abstract	Nicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors. Specifically, the role that sex plays in modulating the effects of nicotine on discrimination learning and cognitive flexibility in rodents is still unclear. Here, we evaluated sex-dependent differences in the effect of daily nicotine intraperitoneal (i.p.) administration at various doses (0.125, 0.25, and 0.5 mg/kg) on visual discrimination (VD) learning and reversal (VDR) learning in mice. In male mice, 0.5 mg/kg nicotine significantly improved performance in the VDR, but not the VD, task, while 0.5 mg/kg nicotine significantly worsened performance in the VD, but not VDR task in female mice. Furthermore, 0.25 mg/kg nicotine significantly worsened performance in the VD and VDR task only in female mice. Next, to investigate the cellular mechanisms that underlie the sex difference in the effects of nicotine on cognition, transcriptomic analyses were performed focusing on the medial prefrontal cortex tissue samples from male and female mice that had received continuous administration of nicotine for 3 or 18 days. As a result of pathway enrichment analysis and protein–protein interaction analysis using gene sets of differentially expressed genes, decreased expression of postsynaptic-related genes in males and increased expression of innate immunity-related genes in females were identified as possible molecular mechanisms related to sex differences in the effects of nicotine on cognition in discrimination learning and cognitive flexibility. Our result suggests that nicotine modulates cognitive function in a sex-dependent manner by alternating the expression of specific gene sets in the medial prefrontal cortex.
Publisher	John Wiley and Sons Inc
Source Title	Journal of Neurochemistry
Volume (Issue)	169(1)
Page	e16227
Date of Issued	2024-09-17
Language	English
Handle URL	https://hdl.handle.net/11094/98306
PISSN	00223042
eISSN	14714159
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/jnc.16227
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of Neurochemistry. 2024, 169(1), p. e16227
DC.title	Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice
DC.creator	Aomine, Yoshiatsu
	Shimo, Yuto
	Sakurai, Koki
	Abe, Mayuka
	Macpherson, Tom
	Ozawa, Takaaki
	Hikida, Takatoshi
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-09-17
DC.identifier	https://doi.org/10.1111/jnc.16227
DC.subject	cognitive flexibility
	protein–protein interaction network
	reversal learning
	RNA-seq
	transcription factor analysis
	visual discrimination learning
DC.description	Aomine Y., Shimo Y., Sakurai K., et al. Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice. Journal of Neurochemistry, (2024); https://doi.org/10.1111/jnc.16227.
DCTERMS.abstract	Nicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors. Specifically, the role that sex plays in modulating the effects of nicotine on discrimination learning and cognitive flexibility in rodents is still unclear. Here, we evaluated sex-dependent differences in the effect of daily nicotine intraperitoneal (i.p.) administration at various doses (0.125, 0.25, and 0.5 mg/kg) on visual discrimination (VD) learning and reversal (VDR) learning in mice. In male mice, 0.5 mg/kg nicotine significantly improved performance in the VDR, but not the VD, task, while 0.5 mg/kg nicotine significantly worsened performance in the VD, but not VDR task in female mice. Furthermore, 0.25 mg/kg nicotine significantly worsened performance in the VD and VDR task only in female mice. Next, to investigate the cellular mechanisms that underlie the sex difference in the effects of nicotine on cognition, transcriptomic analyses were performed focusing on the medial prefrontal cortex tissue samples from male and female mice that had received continuous administration of nicotine for 3 or 18 days. As a result of pathway enrichment analysis and protein–protein interaction analysis using gene sets of differentially expressed genes, decreased expression of postsynaptic-related genes in males and increased expression of innate immunity-related genes in females were identified as possible molecular mechanisms related to sex differences in the effects of nicotine on cognition in discrimination learning and cognitive flexibility. Our result suggests that nicotine modulates cognitive function in a sex-dependent manner by alternating the expression of specific gene sets in the medial prefrontal cortex.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	98306
citation_title	Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice
citation_author	Aomine, Yoshiatsu
	Shimo, Yuto
	Sakurai, Koki
	Abe, Mayuka
	Macpherson, Tom
	Ozawa, Takaaki
	Hikida, Takatoshi
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2024-09-17
citation_journal_title	Journal of Neurochemistry
citation_volume	169
citation_issue	1
citation_firstpage	e16227
citation_doi	https://doi.org/10.1111/jnc.16227
citation_public_url	https://hdl.handle.net/11094/98306

Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice

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