Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation

Sakiyama, Hiroshi; Baba, Kousuke; Kimura, Yasuyoshi; Ogawa, Kotaro; Nishiike, Ujiakira; Hayakawa, Hideki; Yoshida, Miki; Aguirre, Cesar; Ikenaka, Kensuke; Nagano, Seiichi; Mochizuki, Hideki

doi:https://doi.org/10.1016/j.neuint.2024.105906

Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation

Sakiyama, Hiroshi; Baba, Kousuke; Kimura, Yasuyoshi et al.

Neurochemistry International, 2025, 182, 105906

Number of Access:1,587（2025-08-14 15:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100211

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Title	Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation
Creator	NRID 1000040851902 1000040851902 CreatorName Sakiyama, Hiroshi
	NRID 1000090750159 1000090750159 researchmap permalink 5017 5017 Scopus Author ID 7402227089 7402227089 CreatorName Baba, Kousuke
	NRID 1000050727451 1000050727451 ORCID 0000-0001-9147-8058 0000-0001-9147-8058 researchmap permalink y-kimura_neurol y-kimura_neurol Scopus Author ID 56673363900 56673363900 CreatorName Kimura, Yasuyoshi
	NRID 1000080870500 1000080870500 researchmap permalink jihdiegisojosugudc jihdiegisojosugudc Scopus Author ID 57200553653 57200553653 CreatorName Ogawa, Kotaro
	CreatorName Nishiike, Ujiakira
	NRID 1000070468594 1000070468594 researchmap permalink hayahide hayahide Scopus Author ID 7201631140 7201631140 CreatorName Hayakawa, Hideki
	CreatorName Yoshida, Miki
	NRID 1000020865597 1000020865597 researchmap permalink cesarderkatter cesarderkatter CreatorName Aguirre, Cesar
	NRID 1000070774058 1000070774058 researchmap permalink kensukeikenaka kensukeikenaka Scopus Author ID 8588484300 8588484300 CreatorName Ikenaka, Kensuke
	NRID 1000040362727 1000040362727 researchmap permalink read0106301 read0106301 Scopus Author ID 7103321284 7103321284 CreatorName Nagano, Seiichi
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 CreatorName Mochizuki, Hideki
Subject	CC-Chemokine ligand 21
	Neuroinflammation
	Parkinson's disease
	Senescence-accelerated prone 8 (SAMP8) mice
	α-synucleinopathy
Description	Sakiyama H., Baba K., Kimura Y., et al. Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation. Neurochemistry International 182, 105906 (2025); https://doi.org/10.1016/j.neuint.2024.105906.
Abstract	Parkinson's disease (PD) is characterized by the formation of α-synuclein (α-syn) aggregates, which lead to dopaminergic neuronal degeneration. The incidence of PD increases with age, and senescence is considered to be a major risk factor for PD. In this study, we evaluated the effect of senescence on PD pathology using α-synuclein preformed fibrils (PFF) injection model in senescence-accelerated mice. We injected PFF into the substantia nigra (SN) of senescence-accelerated prone 8 (SAMP8) mice and senescence-accelerated resistant 1 (SAMR1) mice. At 24 weeks after injection of saline or PFF, we found that SAMP8 mice injected with PFF exhibited robust Lewy pathology and exacerbated degeneration of dopaminergic neurons in the SN compared to PFF-injected SAMR1 mice. We further observed an increase in the number of Iba1-positive cells in the brains of PFF-injected SAMP8 mice. RNA sequencing revealed that several genes related to neuroinflammation were upregulated in the brains of PFF-injected SAMP8 mice compared to SAMR1 mice. Inflammatory chemokine CC-chemokine ligand 21 (CCL21) was upregulated in PFF-injected SAMP8 mice and expressed in the glial cells of these mice. Our research indicates that accelerated senescence leads to persistent neuroinflammation, which plays an important role in the exacerbation of α-synucleinopathy.
Publisher	Elsevier Ltd
Source Title	Neurochemistry International
Volume (Issue)	182
Page	105906
Date of Issued	2025-01-01
Language	English
Handle URL	https://hdl.handle.net/11094/100211
PISSN	01970186
eISSN	18729754
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.neuint.2024.105906
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 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	Neurochemistry International. 2025, 182, p. 105906
DC.title	Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation
DC.creator	Sakiyama, Hiroshi
	Baba, Kousuke
	Kimura, Yasuyoshi
	Ogawa, Kotaro
	Nishiike, Ujiakira
	Hayakawa, Hideki
	Yoshida, Miki
	Aguirre, Cesar
	Ikenaka, Kensuke
	Nagano, Seiichi
	Mochizuki, Hideki
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-01-01
DC.identifier	https://doi.org/10.1016/j.neuint.2024.105906
DC.subject	CC-Chemokine ligand 21
	Neuroinflammation
	Parkinson's disease
	Senescence-accelerated prone 8 (SAMP8) mice
	α-synucleinopathy
DC.description	Sakiyama H., Baba K., Kimura Y., et al. Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation. Neurochemistry International 182, 105906 (2025); https://doi.org/10.1016/j.neuint.2024.105906.
DCTERMS.abstract	Parkinson's disease (PD) is characterized by the formation of α-synuclein (α-syn) aggregates, which lead to dopaminergic neuronal degeneration. The incidence of PD increases with age, and senescence is considered to be a major risk factor for PD. In this study, we evaluated the effect of senescence on PD pathology using α-synuclein preformed fibrils (PFF) injection model in senescence-accelerated mice. We injected PFF into the substantia nigra (SN) of senescence-accelerated prone 8 (SAMP8) mice and senescence-accelerated resistant 1 (SAMR1) mice. At 24 weeks after injection of saline or PFF, we found that SAMP8 mice injected with PFF exhibited robust Lewy pathology and exacerbated degeneration of dopaminergic neurons in the SN compared to PFF-injected SAMR1 mice. We further observed an increase in the number of Iba1-positive cells in the brains of PFF-injected SAMP8 mice. RNA sequencing revealed that several genes related to neuroinflammation were upregulated in the brains of PFF-injected SAMP8 mice compared to SAMR1 mice. Inflammatory chemokine CC-chemokine ligand 21 (CCL21) was upregulated in PFF-injected SAMP8 mice and expressed in the glial cells of these mice. Our research indicates that accelerated senescence leads to persistent neuroinflammation, which plays an important role in the exacerbation of α-synucleinopathy.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	100211
citation_title	Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation
citation_author	Sakiyama, Hiroshi
	Baba, Kousuke
	Kimura, Yasuyoshi
	Ogawa, Kotaro
	Nishiike, Ujiakira
	Hayakawa, Hideki
	Yoshida, Miki
	Aguirre, Cesar
	Ikenaka, Kensuke
	Nagano, Seiichi
	Mochizuki, Hideki
citation_publisher	Elsevier Ltd
citation_language	English
citation_date	2025-01-01
citation_journal_title	Neurochemistry International
citation_volume	182
citation_firstpage	105906
citation_doi	https://doi.org/10.1016/j.neuint.2024.105906
citation_public_url	https://hdl.handle.net/11094/100211

Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation

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