title: 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.
authors.affiliation: Discipline of Psychiatry, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia 5005, Australia.
authors.forename: Harris
authors.initials: H
authors.lastname: Eyre
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
mesh_terms: D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D003866:Depressive Disorder / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D009473:Neuronal Plasticity / Q000276:immunology*; D009474:Neurons / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha