Toll-like receptors in the depressed and suicide brain

Abstract

Abnormalities of the immune function in depression and suicide are based in part on the observation of increased levels of proinflammatory cytokines in the serum and postmortem brain of depressed and suicidal patients. We have examined if abnormalities of the innate immune receptors, known as Toll-like receptors (TLRs), in the brain are associated with depression and suicide, since the activation of these receptors results in production of cytokines. Of all the TLRs shown to be present in humans, TLR3 and TLR4 appear to be unique and important in brain function. We have determined the protein (by ELISA method) and mRNA expression (using qPCR) of TLR3 and TLR4 in the postmortem brain (dorsolateral prefrontal cortex [DLPFC]) of 22 depressed suicide victims, 11 non-depressed suicide victims, 12 depressed non-suicide subjects and 20 normal control subjects. We found that the mRNA expression of TLR3 and TLR4 was significantly increased in DLPFC of depressed suicide victims and in depressed non-suicide subjects, compared with controls. However, the protein expression of TLR3 and TLR4 was significantly increased in depressed suicide victims, but not in depressed non-suicide subjects compared with controls. The observed abnormalities of proinflammatory cytokines in the brain of suicide victims may be related to an abnormality of TLR3 and TLR4 over-expression. To our knowledge, this is the first study of TLRs in the brain of psychiatric subjects.

Proinflammatory cytokines correlate with early exercise attenuating anxiety‐like behavior after cerebral ischemia

“…Our study found early exercise suppressed glial activity and proinflammatory cytokine expression as well as reducing anxiety‐like behavior. Anxiety‐associated proinflammatory cytokines released from immune cells, as a result of inflammation or stress, have abnormal serum levels in these patients (Pandey, Rizavi, Ren, Bhaumik, & Dwivedi, 2014; Toscano et al, 2016), and increased levels of cytokines contribute to the progress of depression and anxiety (Maldonado‐Bouchard et al, 2016). Our data showed exercise not only reduced the expression of inflammatory cytokines (IL‐6, TNF‐α) of MCAO rats significantly, but also reduced the expression of cell adhesion molecules (ICAM and VCAM), which mediated the leukocyte adhesion and infiltration in response to ischemia reperfusion injury.…”

Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?

“…Peripheral blood gene expression profiles revealed an overexpression of proinflammatory IL-6, IL-8, and type I IFN-induced signaling pathways [104,105,106,107]. Further, increased expression of a variety of innate immune genes and proteins, including IL-1β, IL-6, TNF-α, TLR3, and TLR4, has been found in postmortem brain samples from suicide victims that had depression [108,109]. …”

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Although much of the attention of the literature has been focused on immunologic parameters in the peripheral blood, it should be noted that although the literature is not entirely consistent (Clark et al, 2016), increased activation of microglial cells as well as increased expression of inflammatory cytokines and Toll-like receptors have been described in postmortem brain samples of presumably depressed suicide victims (Steiner et al, 2008(Steiner et al, , 2011Pandey et al, 2012Pandey et al, , 2014Torres-Platas et al, 2014). Inconsistencies in the literature have been attributed to diagnostic considerations, use of medications, brain regions sampled, and small sample sizes.…”