Neuron-Glia Interaction as a Possible Glue to Translate the Mind-Brain Gap: A Novel Multi-Dimensional Approach Toward Psychology and Psychiatry (R1)

Abstract

Neurons and synapses have long been the dominant focus of neuroscience, thus the pathophysiology of psychiatric disorders has come to be understood within the neuronal doctrine. However, the majority of cells in the brain are not neurons but glial cells including astrocytes, oligodendrocytes, and microglia. Traditionally, neuroscientists regarded glial functions as simply providing physical support and maintenance for neurons. Thus, in this limited role glia had been long ignored. Recently, glial functions have been gradually investigated, and increasing evidence has suggested that glial cells perform important roles in various brain functions. Digging up the glial functions and further understanding of these crucial cells, and the interaction between neurons and glia may shed new light on clarifying many unknown aspects including the mind-brain gap, and conscious-unconscious relationships. We briefly review the current situation of glial research in the field, and propose a novel translational research with a multi-dimensional model, combining various experimental approaches such as animal studies, in vitro & in vivo neuron-glia studies, a variety of human brain imaging investigations, and psychometric assessments.

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.…”

Development and validation of the 22‐item Tarumi's Modern‐Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self‐Esteem (TACS‐22)

“…Despite the gradual clarification of the biological aspects of depression, [34][35][36][37][38][39][40] the biological basis of depression-related personality traits has not been well clarified. Tryptophan metabolites, especially serotonin, have gathered greater attention in the endeavor to understand the pathophysiology of depression.…”

Glia‐related genes and their contribution to schizophrenia

“…Human major histocompatibility complex (MHC) is a 4‐million‐base pair (Mb) region located on chromosome 6p21, which contains ∼250 genes and encodes classical HLA genes and other immune genes. MHC class I is found on activated microglia and is involved in complement‐mediated synaptic pruning by microglia . MHC molecules were first investigated because of their ability to identify compatibility for allogeneic tissue grafting.…”

“…MHC class I is found on activated microglia and is involved in complement-mediated synaptic pruning by microglia. 135,136 MHC molecules were first investigated because of their ability to identify compatibility for allogeneic tissue grafting. They play a wider role in immunological reactions and neurodevelopment.…”