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Deep proteome analysis of mouse brains from wild-type, LPS-induced, and drug-treated mice groups

ABSTRACT: We studied the effect of bacterial Lipopolysaccharides on inducing neuroinflammation in mice. In addition, we investigated the effect of novel LAT1-utilizing anti-inflammatory derivatives on reversing this LPS-induced neuroinflammation status. Thus, we performed deep proteome analysis of mouse brains after treatment with vehicle, LPS, and LPS with LAT1-utilizing derivatives. The objective is to follow the different inflammatory biomarkers in the mouse brain and explain the inflammatory process after the LPS treatment with and without the LAT1-utilizing prodrugs.

INSTRUMENT(S): Bruker Daltonics timsTOF series

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Ahmed Montaser

LAB HEAD: Zbyněk Zdráhal

PROVIDER: PXD030838 | Pride | 2022-10-25

REPOSITORIES: Pride

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			Action	DRS
	4583_TIMS2_2col-74m_A2_1_Slot1-10_1_3987.d.7z	Other
	4583_TIMS2_2col-74m_A3_1_Slot1-11_1_4020.d.7z	Other
	4583_TIMS2_2col-74m_A4_1_Slot1-12_1_3991.d.7z	Other
	4583_TIMS2_2col-74m_A5_2_Slot1-13_1_3954.d.7z	Other
	4583_TIMS2_2col-74m_A6_1_Slot1-14_1_4014.d.7z	Other

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Project description:Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections. Experiment Overall Design: In this study, adult and aged mice were injected intraperitoneal with sterile saline or Escherichia coli LPS (0.33 mg/kg, ~10 µg/mouse; serotype 0127:B8, Sigma). This dosage of LPS was used because it induces a mild transient sickness behavior in young adults. Mice were killed 4 h after saline or LPS injection by CO2 asphyxiation. Blood samples were collected and brains were removed, separated in half at the longitudinal fissure, frozen in liquid nitrogen, and stored (-80°C) until assaying. Total RNA was later isolated from some brain samples for microarray analysis (n=3).

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Deep proteome analysis of mouse brains from wild-type, LPS-induced, and drug-treated mice groups

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