Preprint Article Version 3 This version is not peer-reviewed

Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model

Pallavi Shrivastava
,
Yan Lu
,
Shanchun Su
ORCID logo ,
Yuichi Kobayashi
,
Yuhai Zhao
,
Nathan Lien
,
Abdul-Razak Masoud
,
Walter J Lukiw
,
Song Hong
*
Version 1 : Received: 5 July 2024 / Approved: 8 July 2024 / Online: 9 July 2024 (12:24:29 CEST)
Version 2 : Received: 26 September 2024 / Approved: 27 September 2024 / Online: 27 September 2024 (11:49:19 CEST)
Version 3 : Received: 1 November 2024 / Approved: 4 November 2024 / Online: 6 November 2024 (02:46:23 CET)

How to cite: Shrivastava, P.; Lu, Y.; Su, S.; Kobayashi, Y.; Zhao, Y.; Lien, N.; Masoud, A.-R.; Lukiw, W. J.; Hong, S. Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model. Preprints 2024, 2024070723. https://doi.org/10.20944/preprints202407.0723.v3 Shrivastava, P.; Lu, Y.; Su, S.; Kobayashi, Y.; Zhao, Y.; Lien, N.; Masoud, A.-R.; Lukiw, W. J.; Hong, S. Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model. Preprints 2024, 2024070723. https://doi.org/10.20944/preprints202407.0723.v3

Abstract

1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. 2) Methods: Here, we report the effects of long-term treatment with a SPM, maresin like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. 3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in anti-inflammatory Iba1+Arg-1+-M2 microglia, inhibited phenotypic switching to pro-inflammatory N1 neutrophils, promoted the blood–brain-barrier-associated tight-junction protein claudin-5 and decreased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. 4) Conclusion: Long-term administration of MarL1 mitigates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegeneration. These findings provided the preclinical leads and mechanistic insights for the development of MarL1 into an effective modality to ameliorate AD pathogenesis.

Keywords

Maresin-like; Alzheimer's Disease; neuroinflammation; neuropathogenesis; amyloid-β (Aβ); cholinergic neuron; cleaved-caspase-3; M1 or M2 microglia; N1 or N2 neutrophil

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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