Effects of antidepressants on neuroinflammation in models related to dementia
| Drug class | Drug name | Effects |
|---|---|---|
| Tricyclic antidepressants (TCAs) | Amitriptyline | Protects rat cortical neurons against atrophy and synaptic damage induced by TNF-α [62] Inhibits NF-κB translocation to the nucleus and IL-1β production in transgenic mouse model of MSA; reduces gliosis in the hippocampus and basal ganglia [63] |
| Clomipramine | Reduces LPS-stimulated production of NO, IL-1β, and TNF-α in rodent astrocytes and microglia [64] | |
| Imipramine | Reduces LPS-stimulated production of NO, IL-1β, and TNF-α in rodent astrocytes and microglia [64] Inhibits TNF-α and reduces β-amyloid accumulation in a mouse model of AD; protects against memory impairment [65] Inhibits TNF-α-induced expression of CXCL1 in rat astrocytes [66] Increases TGF-β expression and reduces IFN-γ expression in rat hippocampus [67] | |
| Protriptyline | Inhibits NF-κB expression in streptozotocin-induced rat model of AD; improves spatial learning and memory [68] | |
| Selective serotonin reuptake inhibitors (SSRIs) | Fluoxetine | Inhibits NF-κB translocation to the nucleus and IL-1β production in transgenic mouse model of MSA; reduces gliosis in hippocampus and basal ganglia [63] Increases TGF-β expression and reduces IFN-γ expression in rat hippocampus [67] Restores levels of TGF-β and inhibits Aβ-induced oxidative stress in a mouse model of AD; protects against behavioral changes and memory deficits [69] Reduces Aβ-induced toxicity in mixed glia-neuron cultures through conversion of latent to mature TGF-β1 [70] Inhibits LPS-induced production of TNF-α and promotes phagocytosis and autophagy in mouse microglia [71] |
| Sertraline | Inhibits LPS-induced production of TNF-α and increases IL-10 in mouse astrocytes [72] Reduces quinolinic acid-induced elevations in IL-1β, IL-6, and TNF-α and inhibits oxidative stress in a rat model of HD; improves motor functioning [73] | |
| Serotonin-noradrenaline reuptake inhibitors (SNRIs) | Venlafaxine | Reduces quinolinic acid-induced elevations in IL-1β, IL-6, and TNF-α and inhibits oxidative stress in a rat model of HD; improves motor functioning [73] |
| Monoamine oxidase inhibitors (MAOIs) | Moclobemide | Reduces LPS-induced expression of IL-1β and TNF-α in rat mixed glial cells [74] |
| Phenelzine | Increases TGF-β expression and reduces IFN-γ expression in rat hippocampus [67] | |
| Tranylcypromine | Reduces LPS-induced expression of IL-1β IL-6, reduces p-STAT3 and NF-κB nuclear translocation, and reduces TLR4/ERK signaling in mouse microglia; downregulates Aβ-induced microglial activation in a mouse model of AD [75] | |
| Others | Tianeptine | Reduces gp120-induced apoptosis and stimulation of caspase-3, suppresses NOS, and inhibits NF-κB transcription in human astroglial cells [76] Inhibits expression of plasminogen activator inhibitor-1 (Serpine-1) and reduces lipid peroxidation and apoptosis in mouse cortical neurons exposed to oxygen-glucose deprivation [77] |
| Trazodone | Reduces microglial NLRP3 inflammasome expression, phosphorylated p38 MAPK and ATF4 levels, and tau levels in a mouse model of tauopathy; improves sleep and memory [81] | |
| Vortioxetine | Restores levels of TGF-β and inhibits Aβ-induced oxidative stress in a mouse model of AD; protects against behavioral changes and memory deficits [69] Reduces caspase-3 expression and α-synuclein deposition in a rotenone-induced rat model of PD; improves motor, cognitive, and behavioral functioning [78] | |
| Agomelatine | Reduces expression of aging-related proteins, caspase-3, and glutamate-included excitotoxicity; stabilizes endoplasmic reticulum and mitochondrial membranes in a rat model of aging [79] |
Aβ: amyloid-beta protein; ATF4: activating transcription factor 4; CXCL1: chemokine ligand 1; ERK: extracellular signal-regulated kinase; gp120: glycoprotein 120; HD: Huntington’s disease; IFN-γ: interferon-gamma; MAPK: mitogen-activated protein kinase; LPS: lipopolysaccharide; MSA: multiple systems atrophy; NF-κB: nuclear factor kappa B; NLRP3: Nod-like receptor protein 3; NO: nitric oxide; NOS: NO synthase; PD: Parkinson’s disease; p-STAT3: phosphorylated signal transducer and activator of transcription protein 3; TGF-β: transforming growth factor-beta; TLR4: toll-like receptor 4
