Neuroplastic changes in depression: A role for the immune system
Abstract
Accumulating evidence suggests that there is a rich cross-talk between the neuroimmune system and neuroplasticity mechanisms under both physiological conditions and pathophysiological conditions in depression. Anti-neuroplastic changes which occur in depression include a decrease in proliferation of neural stem cells (NSCs), decreased survival of neuroblasts and immature neurons, impaired neurocircuitry (cortical-striatal-limbic circuits), reduced levels of neurotrophins, reduced spine density and dendritic retraction. Since both humoral and cellular immune factors have been implicated in neuroplastic processes, in this review we present a model suggesting that neuroplastic processes in depression are mediated through various neuroimmune mechanisms. The review puts forward a model in that both humoral and cellular neuroimmune factors are involved with impairing neuroplasticity under pathophysiological conditions such as depression. Specifically, neuroimmune factors including interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, CD4⁺CD25⁺T regulatory cells (T reg), self-specific CD4⁺T cells, monocyte-derived macrophages, microglia and astrocytes are shown to be vital to processes of neuroplasticity such as long-term potentiation (LTP), NSC survival, synaptic branching, neurotrophin regulation and neurogenesis. In rodent models of depression, IL-1, IL-6 and TNF are associated with reduced hippocampal neurogenesis; mechanisms which are associated with this include the stress-activated protein kinase (SAPK)/Janus Kinase (JNK) pathway, hypoxia-inducible factors (HIF)-1α, JAK-Signal Transducer and Activator of Transcription (STAT) pathway, mitogen-activated protein kinase (MAPK)/cAMP responsive element binding protein (CREB) pathway, Ras-MAPK, PI-3 kinase, IKK/nuclear factor (NF)-κB and TGFβ activated kinase-1 (TAK-1). Neuroimmunological mechanisms have an active role in the neuroplastic changes associated with depression. Since therapies in depression, including antidepressants (AD), omega-3 polyunsaturated fatty acids (PUFAs) and physical activity exert neuroplasticity-enhancing effects potentially mediated by neuroimmune mechanisms, the immune system might serve as a promising target for interventions in depression.
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IL-6 and TNF-α may reduce hippocampal synaptic plasticity.
“In addition, IL-6 and TNF-α may reduce hippocampal synaptic plasticity [37].”
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“A link between immune dysregulation and the pathophysiology of at least some forms of major affective disorder has long been hypothesized and abnormalities in peripheral cytokines in depressed patients have led to propose a primary immunological etiology for MDD (Eyre and Baune, 2012).”
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Self-citation
- Authors
- Eyre, H., & Baune, B. T.
- Affiliations
- The University of Adelaide (AU)
- Corresponding author
- Baune, Bernhard T.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 37
- Issue
- 9
- Pages
- 1397-1416
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W1990487655
- Cited by
- 319
- References
- 285
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 15 · 2023: 18 · 2022: 21 · 2021: 15 · 2020: 25 · 2019: 23 · 2018: 30 · 2017: 21 · 2016: 23 · 2015: 28 · 2014: 31 · 2013: 27 · 2012: 11
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Health and Medical Research Council Australia (APP1003788)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, neuroplasticity, neuroimmune system, neurogenesis, hippocampal neurogenesis, neural stem cells, neurotrophins, interleukin-1, interleukin-6, TNF-α, regulatory T cells, microglia, astrocytes, macrophages, synaptic plasticity, long-term potentiation, JNK signaling, NF-κB signaling, antidepressants, omega-3 polyunsaturated fatty acids, physical activity, neuroinflammation
- MeSH terms
- Brain, Depressive Disorder, Humans, Interleukin-1, Lymphocytes, Neuronal Plasticity, Neurons, Tumor Necrosis Factor-alpha, Interleukin-6
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