Role of Microglial M1/M2 Polarization in Relapse and Remission of Psychiatric Disorders and Diseases

Abstract

Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS). In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress

“…IL-10 is a cytokine that reflects M2 polarization of microglia and its synthesis and release inhibits the production of proinflammatory cytokines by M1 microglia [41]. Increased IL-10 levels have been found in the cerebrospinal fluid of patients with schizophrenia [42], but the stimulatory effect of paliperidone on IL-10 mRNA levels in PFC samples shown herein needs to be corroborated in the cerebrospinal fluid or postmortem brain tissue of patients treated with risperidone/ paliperidone or other antipsychotics.…”

“…In addition, some antipsychotics inhibit the release of nitric oxide and cytokines from activated microglial cells, possibly through the suppression of [Ca 2+ ]i elevation in microglial cells [43,52]. Thus, there is a growing perception of the role of microglia in the pathophysiology of schizophrenia and other stress-related psychiatric diseases, as well as the regulatory role of antipsychotics on microglia activation and possibly polarization to other anti-inflammatory profiles in different states of the natural course of the disease [41].…”

Repeated mild traumatic brain injury: potential mechanisms of damage

“…182 Alternatively, microglia can assume a reparative role by releasing anti-inflammatory cytokines such as IL-10 that inhibit proinflammatory functions. 189 Numbers of microglia along the cell death (M1) and repair promoting (M2) phenotypic spectrum depend on TBI severity and kinetics of regulation. 188,190 The "immunoexcitotoxicity" theory suggests an alternative to the traditional and functionally distinct M1-M2 phenotypic polarization.…”

Imaging robust microglial activation after lipopolysaccharide administration in humans with PET

“…However, studies examining TSPO expression between healthy control subjects and other patient groups such as multiple sclerosis, depression, or cocaine abusers (23)(24)(25)(26)(27) have produced mixed results. A well-established and robust preclinical model uses the administration of Escherichia coli lipopolysaccharide (LPS; also called endotoxin) to trigger "classic" activation of microglia and has been used in rodents to study neurodegeneration (28)(29)(30)(31). We previously reported a significant increase in [ 11 C]PBR28 binding at 1 (29%) and 4 (62%) hours after LPS administration in nonhuman primates (NHPs) compared with baseline binding levels (32).…”