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Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism
journal contribution
posted on 2023-06-08, 17:11 authored by Neil Harrison, Christian F Doeller, Valerie Voon, Neil Burgess, Hugo CritchleyHugo CritchleyBACKGROUND Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. METHODS Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. RESULTS Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. CONCLUSIONS These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease.
Funding
The Wellcome Trust
History
Publication status
- Published
File Version
- Accepted version
Journal
Biological PsychiatryISSN
0006-3223Publisher
ElsevierExternal DOI
Issue
7Volume
76Page range
585-593Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2014-05-07First Open Access (FOA) Date
2014-07-31First Compliant Deposit (FCD) Date
2014-07-31Usage metrics
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