HDL and LDL have distinct, opposing effects on LPS-induced brain inflammation

Radford-Smith, DE; Yates, AG; Rizvi, L; Anthony, DC; Probert, F

Journal article

HDL and LDL have distinct, opposing effects on LPS-induced brain inflammation

Abstract:: CNS inflammation, including microglial activation, in response to peripheral infections are known to contribute to the pathology of both familial and sporadic neurodegenerative disease. The relationship between Fused-in-Sarcoma Protein (FUS)-mediated disease in the transgenic FUS[1–359] animals and the systemic inflammatory response have not been explored. Here, we investigated microglial activation, inflammatory gene expression and the behavioural responses to lipopolysaccharide-induced (LPS; 0.1 mg/kg) systemic inflammation in the FUS[1–359] transgenic mice. The pathology of these mice recapitulates the key features of mutant FUS-associated familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Here, pre-symptomatic 8-week-old mutant or wild type controls were challenged with LPS or with saline and sucrose intake, novel cage exploration, marble burying and swimming behaviours were analyzed. The level of pro-inflammatory gene expression was also determined, and microglial activation was evaluated. In chronic experiments, to discover whether the LPS challenge would affect the onset of ALS-like paralysis, animals were evaluated for clinical signs from 5 to 7 weeks post-injection. Compared to controls, acutely challenged FUS[1–359]-tg mice exhibited decreased sucrose intake and increased floating behaviours. The FUS[1–359]-tg mice exhibited an increase in immunoreactivity for Iba1-positive cells in the prefrontal cortex and ventral horn of the spinal cord, which was accompanied by increased expression of interleukin-1β, tumour necrosis factor, cyclooxygenase-(COX)-1 and COX-2. However, the single LPS challenge did not alter the time to development of paralysis in the FUS[1–359]-tg mice. Thus, while the acute inflammatory response was enhanced in the FUS mutant animals, it did not have a lasting impact on disease progression

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Radford-Smith, D. E., Yates, A. G., Rizvi, L., Anthony, D. C., & Probert, F. (2023). HDL and LDL have distinct, opposing effects on LPS-induced brain inflammation. Lipids in Health and Disease, 22(1), 54–54.

MLA Style

Radford-Smith, DE, et al. “HDL and LDL Have Distinct, Opposing Effects on LPS-Induced Brain Inflammation.” Lipids in Health and Disease, vol. 22, no. 1, 2023, pp. 54–54.

Chicago Style

Radford-Smith, DE, AG Yates, L Rizvi, DC Anthony, and F Probert. 2023. “HDL and LDL Have Distinct, Opposing Effects on LPS-Induced Brain Inflammation.” Lipids in Health and Disease 22 (1): 54–54.
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