Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder

Abstract

The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography studies have indicated microglial overactivation in the brain of patients with bipolar disorder. We have recently developed a technique to induced microglia-like (iMG) cells from peripheral blood (monocytes). We introduce a novel translational approach focusing on bipolar disorder using this iMG technique. We hypothesize that immunological conditional changes in microglia may contribute to the shift between manic and depressive states, and thus we herein analyzed gene profiling patterns of iMG cells from three patients with rapid cycling bipolar disorder during both manic and depressive states, respectively. We revealed that the gene profiling patterns are different between manic and depressive states. The profiling pattern of case 1 showed that M1 microglia is dominant in the manic state compared to the depressive state. However, the patterns of cases 2 and 3 were not consistent with the pattern of case 1. CD206, a mannose receptor known as a typical M2 marker, was significantly downregulated in the manic state among all three patients. This is the first report to indicate the importance of shifting microglial M1/M2 characteristics, especially the CD206 gene expression pattern between depressive and manic states. Further translational studies are needed to dig up the microglial roles in the underlying biological mechanisms of bipolar disorder.

HLA genetics in bipolar disorder

“…It is worth mentioning the pioneering work of Ohgidani et al., showing, using microglial‐like cells derived from peripheral monocytes, that the proinflammatory M1 microglia is dominant in the manic as compared with depressive state . Although, we have no direct evidence relating HLA genetics to microglial polarization, our finding concerning genetic association of 57.1 and 8.1 haplotypes (inflammatory haplotypes) with rapid cycling may be pertinent.…”

Hikikomori : Multidimensional understanding, assessment, and future international perspectives

“…On the basis of such pilot investigations, we have hypothesized that inflammation and oxidative stress may be linked to the underlying pathophysiology of hikikomori , similarly to other psychiatric disorders . Microglia play crucial roles in brain inflammation via releasing free radicals and inflammatory cytokines, such as interleukin‐6 and tumor necrosis factor‐α, and activation of microglia has recently been proposed to exist in various psychiatric disorders, including schizophrenia, depression, bipolar disorder, and autism . In addition, microglial overactivation is proposed to exist in the brains of suicide victims and suicidal individuals, especially via the tryptophan–kynurenine pathway .…”

“…76,[83][84][85][86][87] Microglia play crucial roles in brain inflammation via releasing free radicals and inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, 88,89 and activation of microglia has recently been proposed to exist in various psychiatric disorders, including schizophrenia, depression, bipolar disorder, and autism. 76,86,[90][91][92][93][94][95][96][97] In addition, microglial overactivation is proposed to exist in the brains of suicide victims and suicidal individuals, especially via the tryptophan-kynurenine pathway. [98][99][100][101][102][103] As noted above, a recent epidemiological data analysis showed that hikikomori sufferers are more likely to have suicide risk, 29 thus similar biological mechanisms via microglial activation may exist in hikikomori.…”

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

“…The pathophysiology of BD is yet to be well understood, while recent studies have indicated that abnormal immunological functions may be a contributing factor [38][39][40][41][42]. Recently, positron emission tomography (PET) studies have shown microglial overactivation in the brain of patients with various psychiatric disorders [43][44][45]; [9] including bipolar disorder [42].…”

“…The pathophysiology of BD is yet to be well understood, while recent studies have indicated that abnormal immunological functions may be a contributing factor [38][39][40][41][42]. Recently, positron emission tomography (PET) studies have shown microglial overactivation in the brain of patients with various psychiatric disorders [43][44][45]; [9] including bipolar disorder [42]. Consistent with the previous studies, it was revealed that in BD, the immune system is chronically activated by microglia, which in turn produces cytokines that render the brain to a vulnerable and unstable state, precipitating mood disturbances [45][46][47].…”