Pomara, N;
Bruno, D;
Plaska, CR;
Pillai, A;
Ramos-Cejudo, J;
Osorio, R;
Imbimbo, BP;
... Blennow, K; + view all
(2021)
Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression.
Journal of Affective Disorders
, 286
pp. 275-281.
10.1016/j.jad.2021.03.012.
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Abstract
BACKGROUND: Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) mechanism contributed to increased neuroinflammation observed in depression. METHODS: We measured cerebrospinal fluid (CSF) cholinergic markers (AChE and BChE activities) in 28 individuals with longstanding late-life major depression (LLMD) and 19 controls and their relationship to central and peripheral levels of pro-inflammatory cytokines (IL-6 and IL-8). Additionally, we examined if these cholinergic indices were related to CSF markers of microglial activation and neuroinflammation (sTREM2 and complement C3). RESULTS: Compared with controls, LLMD patients had a significant reduction in CSF BChE levels. Lower CSF BChE and AChE activities were associated with lower CSF markers of microglial and neuroinflammation (sTREM2 and C3). In addition, in LLMD patients we found an inverse relationship between peripheral marker of inflammation (plasma IL-6) and CSF BChE and AChE levels. CONCLUSIONS: Our results suggest an upregulation of the CAP mechanism in LLMD with an elevation in peripheral markers of inflammation and concomitant reduction in markers of glial activation associated with a higher cholinergic tone. Future studies should confirm these findings in a larger sample including individuals with acute and more severe depressive episodes and across all ages.
| Type: | Article |
|---|---|
| Title: | Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jad.2021.03.012 |
| Publisher version: | https://doi.org/10.1016/j.jad.2021.03.012 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Acetylcholinesterase, Butyrylcholinesterase, C3, Cerebrospinal fluid, Cholinergic anti-inflammatory pathway, Late-life major depression |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10126216 |
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