Neuroinflammation is an inflammatory response within the brain or spinal cord.
Depressed patients present increased plasma levels of lipopolysaccharide (LPS) and neuroinflammatory alterations.
Male rats received amitriptyline (AMI) a tricyclic, S-citalopram (ESC) a selective serotonin reuptake inhibitor, tranylcypromine (TCP) a monoamine oxidase inhibitor, vortioxetine (VORT) a multimodal AD or saline for ten days.
Lipopolysaccharide (LPS) induces despair-like, impaired motivation/self-care behavior, and caused anhedonia.
All ADs prevented LPS-induced despair-like behavior.
Only VORT rescued impaired self-care behavior.
All ADs prevented LPS-induced increase in brain pro-inflammatory cytokines [interleukin (IL)-1β and IL-6] and T-helper 1 cytokines [tumor necrosis factor (TNF)-α and interferon-γ].
VORT increased striatal and hypothalamic IL-4 levels.
All ADs prevented LPS-induced neuroendocrine alterations, represented by increased levels of hypothalamic nitrite and plasma corticosterone response.
VORT and ESC prevented LPS-induced increase in NF-kBp65 hippocampal expression.
ESC, TCP, and VORT, but not IMI, prevented the alterations in phospho-CREB expression.
Inflammation is regulated by pro-inflammatory cytokines and chemokines that are expressed by immune and non-immune cells. Their dysregulation is a hallmark of chronic inflammatory and autoimmune diseases. Significant evidence supports that monoamine oxidase (MAO) inhibitor drugs have anti-inflammatory effects. MAO inhibitors are principally prescribed for the management of a variety of central nervous system (CNS)-associated diseases such as depression, Alzheimer's, and Parkinson's; however, they also have anti-inflammatory effects in the CNS and a variety of non-CNS tissues. To bolster support for their development as anti-inflammatories, it is critical to elucidate their mechanism(s) of action.
MAO inhibitors decrease the generation of end products such as:
They also inhibit biogenic amine degradation, and this increases cellular and pericellular catecholamines in a variety of immune and some non-immune cells. This decrease in end product metabolites and increase in catecholamines can play a significant role in the anti-inflammatory effects of MAO inhibitors.
Irreversible and reversible MAO-A, MAO-B, and MAO-A/B inhibitors have all been shown to significantly reduce inflammation-associated cytokine and chemokine gene and protein expression in a variety of cell cultures and animal studies.
https://www.sciencedirect.com/science/article/abs/pii/S0165032719326539
https://www.frontiersin.org/articles/10.3389/fphar.2021.676239/full