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

アクセス数:1,638件（2025-09-05 01:30 集計）

固定URL: https://hdl.handle.net/11094/100211

閲覧可能ファイル

ファイル	フォーマット	利用条件	サイズ	閲覧回数	利用開始日	説明	information
NeurochemInt_182_105906	pdf	なし	5.79 MB	41	2025.02.06

Creative Commons : 表示 - 非営利

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

タイトル	Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation
著者	NRID 1000040851902 1000040851902 著者名 Sakiyama, Hiroshi
	NRID 1000090750159 1000090750159 researchmap permalink 5017 5017 Scopus Author ID 7402227089 7402227089 著者名 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 著者名 Kimura, Yasuyoshi
	NRID 1000080870500 1000080870500 researchmap permalink jihdiegisojosugudc jihdiegisojosugudc Scopus Author ID 57200553653 57200553653 著者名 Ogawa, Kotaro
	著者名 Nishiike, Ujiakira
	NRID 1000070468594 1000070468594 researchmap permalink hayahide hayahide Scopus Author ID 7201631140 7201631140 著者名 Hayakawa, Hideki
	著者名 Yoshida, Miki
	NRID 1000020865597 1000020865597 researchmap permalink cesarderkatter cesarderkatter 著者名 Aguirre, Cesar
	NRID 1000070774058 1000070774058 researchmap permalink kensukeikenaka kensukeikenaka Scopus Author ID 8588484300 8588484300 著者名 Ikenaka, Kensuke
	NRID 1000040362727 1000040362727 researchmap permalink read0106301 read0106301 Scopus Author ID 7103321284 7103321284 著者名 Nagano, Seiichi
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 著者名 Mochizuki, Hideki
キーワード等	CC-Chemokine ligand 21
	Neuroinflammation
	Parkinson's disease
	Senescence-accelerated prone 8 (SAMP8) mice
	α-synucleinopathy
内容	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.
抄録	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.
出版者	Elsevier Ltd
収録物名	Neurochemistry International
巻(号)	182
ページ	105906
刊行年月	2025-01-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/100211
PISSN	01970186
eISSN	18729754
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.neuint.2024.105906
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
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	英語
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	英語
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

閲覧可能ファイル

論文情報

論文詳細を表示