Cited by 319Tryptophan and brain disordersNeurogenesis and neuroplasticity mechanismsStress Responses and Cortisol

Neuroplastic changes in depression: A role for the immune system

Eyre, Harris, Baune, Bernhard T.·2012·Psychoneuroendocrinology

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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Crossref · 10.1016/j.psyneuen.2012.03.019

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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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