Cognitive dysfunction is associated with systemic inflammation and neuroinflammation in a rodent model of NASH

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Background: Impaired cognition is well recognized in non-alcoholic fatty liver disease (NAFLD) and may affect up to 70% of NAFLD patients. The aim of this study was to investigate the hypothesis that cognitive dysfunction results from systemic and neuroinflammation in experimental NAFLD.
Methods: Twenty male Sprague Dawley rats were fed a high-fat, high-cholesterol (HFHC) diet to induce NAFLD or a standard diet (n = 10 per group), for 16 weeks. The animals were studied for: behavioural changes - using validated neuropsychological tests; systemic inflammation - with a broad panel of plasma cytokines; neuroinflammation - using [3H]PK11195 brain autoradiography.
Results: The HFHC diet induced NASH with extensive steatosis and lobular inflammation but no fibrosis. The HFHC rats demonstrated clear behavioural changes compared with standard diet: in Porsolt’s Swim Test, they showed a depressive-like behaviour evidenced by increased immobility (p = 0.011) and reduced time swimming (p = 0.031); in the Novel Object Recognition test, they displayed impaired memory of previously encountered objects (p = 0.047). These changes were associated with elevated plasma pro-inflammatory cytokines (IFN-γ, GRO/KC, IL-1a, IL-2, IL-6, IL-10, IL-13, IL-17, MIP-1a, RANTES and MCP-1 (all p < 0.05)) and, importantly, with increased microglia activation, demonstrated by increased specific-binding of [3H]PK11195 in the prefrontal cortex (p < 0.05).
Conclusion: Our data affirms that cognitive changes are present in preclinical NASH, even before fibrosis progression, and this is accompanied by systemic and neuroinflammation. The mechanistic pathways linking systemic and neuroinflammation require further elucidation, to highlight targets for therapy in patients.
Original languageEnglish
Publication year7 Oct 2021
Publication statusPublished - 7 Oct 2021
EventISHEN 2021 SYMPOSIUM -
Duration: 6 Oct 20218 Oct 2021
https://www.ishen2021.org/

Conference

ConferenceISHEN 2021 SYMPOSIUM
Period06/10/202108/10/2021
Internet address

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