Chronic peripheral inflammation, hippocampal neurogenesis, and behavior
Open accessAbstract
Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients.
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Peripheral pro-inflammatory cytokines can activate brain microglia and lead to lower hippocampal neurogenesis.
“the stimulating effects of peripheral pro-inflammatory cytokines on brain microglia can result in reduced hippocampal neurogenesis (92).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [92]
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Stanojcic, M., Burstyn‐Cohen, T., Nashi, N., Lemke, G., & Šakić, B. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.05.061 · Cited by 28 · see citing works
Cognitive disorders in diabetic patients
Koekkoek, P. S., Rutten, G. E. H. M., & Biessels, G. J. (2014) · Handbook of clinical neurology · doi:10.1016/b978-0-444-53480-4.00011-4 · Cited by 24 · see citing works
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Belleau, E. L., Treadway, M. T., & Pizzagalli, D. A. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.09.031 · Cited by 550 · see citing works
Wang, Y.-L., Han, Q.-Q., Gong, W.-Q., Pan, D.-H., Wang, L.-Z., Hu, W., Yang, M., Li, B., Yu, J., & Liu, Q. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1054-3 · Cited by 438 · see citing works
The menace of obesity to depression and anxiety prevalence
Fulton, S., Décarie-Spain, L., Fioramonti, X., Guiard, B., & Nakajima, S. (2022) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.10.005 · Cited by 441 · see citing works
“High-fat feeding triggers hippocampal proinflammatory marker upregulation that can elicit depressive-like behavior, reduce neurogenesis, and impair hippocampal function [102].”
BackgroundSun, X.-Y., Zheng, T., Yang, X., Liu, L., Gao, S.-S., Xu, H.-B., Song, Y.-T., Tong, K., Yang, L., Gao, Y., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1640-z · Cited by 59 · see citing works
Unified theory of Alzheimer’s disease (UTAD): implications for prevention and curative therapy
Nehls, M. (2016) · Journal of Molecular Psychiatry · doi:10.1186/s40303-016-0018-8 · Cited by 41 · see citing works
Meta-analysis of molecular imaging of translocator protein in major depression
Eggerstorfer, B., Kim, J.-H., Cumming, P., Lanzenberger, R., & Gryglewski, G. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.981442 · Cited by 35 · see citing works
Neurogenesis and Neuroinflammation in Dialogue: Mapping Gaps, Modulating Microglia, Rewiring Aging
Tanaka, M. (2026) · Cells · doi:10.3390/cells15010078 · Cited by 11 · see citing works
- Authors
- Chesnokova, V., Pechnick, R. N., & Wawrowsky, K.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Western University of Health Sciences (US)
- Corresponding author
- Chesnokova, Vera
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 58
- Pages
- 1-8
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4956598
- OpenAlex
- W2275191480
- Cited by
- 299
- References
- 101
- Citations by year
- 2026: 34 · 2025: 48 · 2024: 24 · 2023: 37 · 2022: 29 · 2021: 36 · 2020: 25 · 2019: 22 · 2018: 17 · 2017: 17 · 2016: 9
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (MH79988)
- NARSAD Independent Investigator Award
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- adult hippocampal neurogenesis, hippocampal neurogenesis, inflammatory cytokines, microglia, neuroinflammation, cognitive impairment, learning and memory, depression, anxiety, mood disorders
- MeSH terms
- Aging, Animals, Diabetes Mellitus, Enterocolitis, Hippocampus, Humans, Inflammation, Lupus Erythematosus, Systemic, Obesity, Diabetes Complications, Neurogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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