Review Article
Volume 2 Issue 4 - 2018
Discrepancy in Microglia and Peripheral Monocytic Cells, a Scope in the Pathophysiology of Psychiatric Maladies
Jes Paul*
Department of molecular and cellular physiology, Albany Medical College, Albany, NY, USA
*Corresponding Author: Jes Paul, Department of molecular and cellular physiology, Albany Medical College, Albany, NY, USA.
Received: June 10, 2018; Published: July 06, 2018
Broad medleys of research have recognized the microglial activation in perilous psychiatric maladies such as schizophrenia, bipolar disorder, and major depressive disorder. There is a scenario of enlivening of peripheral monocytic cells along with the microglial interactions within the body while considering the Pathogenisis of psychiatric disorders. this review, epitomize and discuss the activation of microglia and monocytic cells in psychiatric disorders, thereby showcasing the potential association between these cell types and the Pathogenisis of the ailment, and proffer perspectives for future research on these processes.
In a variation of psychiatric disorders suchlike schizophrenia, bipolar disorder and major depressive disorder, a diversity of postmortem brain studies and recent positron emission tomography (PET)-based studies indicated an association between alterations in monocytic features and psychiatric disorders (Theodoropoulou., et al. 2001:Padmos., et al. 2008; Drexhage., et al. 2011).
In the course of pathological conditions, monocytes are initiated from peripheral blood into the brain, where they collaborate with microglia in immune responses (Beumer., et al. 2012; Shechter and Schwartz, 2013; Prinz and Priller, 2014). peripheral monocytes have the capability to set apart into macrophages and dendritic cells in peripheral tissues, which share resemblance with microglia in their cellular morphology and roles, such as phagocytic activities, uniform gene expression profiles and the locution of cell surface markers and cytokine genesis (Schmitz., et al. 2009; Beumer., et al. 2012Shechter and Schwartz, 2013Prinz and Priller, 2014). This review airs the potential mechanisms linking microglial and monocytic activation with the pathogenesis of psychiatric disorders. Also it portrays and propose directions for future research on these potential associations.
Recent findings
Numerous Postmortem brain studies have unveiled the link between psychiatric disorders and microglial activation (Bayer., et al. 1999; Radewicz., et al. 2000; Tang., et al. 2012Fillman., et al. 2013Hercher., et al. 2014Torres-Platas., et al. 2014).
Activated microglial cells were speculated to be increased in prefrontal white matter from patients with schizophrenia, but not that from patients with bipolar disorder while the qualitative assessment of microglial morphology is done. Hercher., et al. (2014) . Radewicz., et al. (2000) disclosed that in immunostaining studies the expression of Human Leukocyte Antigen-antigen D Related (HLA-DR), which reacts with activated microglia, was inflated in the frontal cortices of patients with schizophrenia. antigen-presenting cells) was increased in the white matter of patients with schizophrenia as per Fillman., et al. (2013) .positive correlations such as changes in the expression of genes that encode markers of activated microglia are seen among the several activated microglial markers in subjects with schizophrenia. (i.e.  Tang., et al. (2012)). 
Pathogenesis of Psychiatric chaos
Microglial Function and Potential Mechanisms is the mess in Psychiatric Upset. Hematopoietic stem cells in the yolk sac in the early developmental stage is the genesis of Microglia which comprise ~12% of cells in the central nervous system (CNS); These cells are not analogously dispersed (Schmitz., et al. 2009). More microglia are sited close to neurons in the gray matter, with the peaked concentrations in the hippocampus, olfactory telencephalon, basal ganglia, and substantia nigra.
Pile of evidence from fate-mapping studies allude to the origin of most microglia is not the bone marrow after birth but hematopoietic stem cells in the yolk sac in the early developmental stage (Lassmann., et al. 1993Ginhoux., et al. 2010Schulz., et al. 2012Kierdorf., et al. 2013Prinz and Priller, 2014). Novel transgenic approaches have shown clear differences in the cellular characteristics of microglia and macrophages in the brain (Goldmann., et al. 2013Parkhurst., et al. 2013Yona., et al. 2013).
In contrast to macrophages, microglia are long-lived and are not replaced by circulating peripheral monocytes under physiological conditions. by various pathological conditions, such as trauma, infection, or other damage to brain tissue Activated microglia retract their cellular processes and transform from a ramified state into an ameboid morphology, Activated microglial functions include phagocytosis and the fabrica1tion and discharge of cytokines, reactive oxygen species and nitrogen species (Barger and Basile, 2001Takaki., et al. 2012Réus., et al. 2015).
Potential Pathogenic Mechanisms Underlying the Involvement of Peripheral Monocytes in Psychiatric Disorders
Being the precursors of tissue macrophages, osteoclasts, and antigen-presenting cells the Monocytes are differentiated in to five subsets based on the different surface markers (Lawson., et al. 1990;Schmitz and Grandl, 2007). (Schmitz., et al. 1997Stöhr., et al. 1998Rothe., et al. 1999Gordon and Taylor, 2005Beumer., et al. 2012). Almost half of them corresponds to subset 1 and are characterized by surface marker profiles with abundant CD14 and a lack of CD16 expression. Both subsets 2 and 3 have CD16 expression and comprise active phagocytic cells in common but differs in the expression of CD14. Increased expression of CD14 is seen in subset 2 compared with subset 3.
Subset 4 is a precursor of dendritic cells with high expression of CD40. While Subset 5, the smallest subset, even though it shares many surface markers with subset 1; however, it differs in the additional expression of CD56, a marker of immature monocytes. Conversation between subsets among peripheral monocytes can arise concomitant with the demarcation of microglia in the brain under certain pathogenic conditions allied to psychiatric diseases, although these potentialities remain to be clarified.
Virtual Mechanisms Linking Arousal of Microglial and Peripheral Monocytic Cells to Psychiatric Disorder
Parallel responses are manifested by both microglia and monocytes to systemic stimuli. These two cell types evince alike profiles for cytokine production, such as interleukin (IL) 1β, IL-6, IL-8 or tumor necrosis factor (TNF)-α. They also show likeness in surface markers, such as cluster of differentiation 14 (CD14), major histocompatibility complex (MHC) molecules, and chemokine receptors.
In response to Local stimuli in the brain, the circulating monocyte-derived macrophage/dendritic cells are pledged into the central nervous system (CNS). Immigrant monocytic cells, which have concise life span may collude with microglia in the innate immune response. Signals are transduced between microglia and circulating monocytes via the blood-brain barrier (BBB). Biological reactions are advertised through neuronal signal transduction. Microglia and peripheral monocytic cells may also wield related Peripheral inflammation.
Reaction of Microglia and Peripheral Monocytic Cells to Stimuli (Endogenous or Exogenous)
As cited in the introduction, microglia and monocytes have concordant purpose such as phagocytosis and the discharge of pro-inflammatory cytokines, as well as parallel expression of surface markers, such as CD14, MHC molecules, and chemokine receptors (Schmitz., et al. 2009Beumer., et al. 2012Shechter and Schwartz, 2013Prinz and Priller, 2014). Schmitz., et al. (2009) detected over-representation of genes connected with Alzheimer’s disease among the expression profiles specific to microglia and monocytes (Lutter., et al. 2008).All these studies when taken together ,it bespeaks that microglia and monocytes have harmonious gene expression pattern under normal conditions; however, there occur changes in the pattern of countenance profiles in response to stimuli are quite different.
Neuropsychoimmune interactions in the pathophysiology of psychiatric disorders (Innate Immune Response)
Detriment to the CNS (central nervous system) habitually ends in the enrollment of circulating immune cells, including monocytes, which ensue in an innate immune response that consists of microglia and monocyte-derived macrophages/dendritic cells (Prinz and Priller, 2014). In disorders like Alzheimer’s disease, triggered microglia have been kindred with amyloid-β-induced neurotoxicity, and microglia were also injured by amyloid species (Simard., et al. 2006Mildner., et al. 2011Prinz and Priller, 2014). Likewise the rectification from spinal cord injury in mice has been reported to rest more on infiltrating monocyte-derived macrophages than on resident microglia (J Paul., et al. 2010).
Interactions through the Blood-Brain Barrier and Synergy through Neuronal Networking
Synergy between microglia and monocytes are governed by cytokines. Even though both microglia and monocytes are actuated by and exempt pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8 or TNF-α (Schmitz., et al. 2009Beumer., et al. 2012), as the cytokines are relatively large molecules and rarely cross the blood-brain barrier (BBB). But there are some agencies and routes by which they can cross the barrier, such as variances in the barrier’s permeability, crossway though circumventricular organs, or the use of precise transporters or receptors (Banks and Erickson, 2010).
Moreover, many Studies have proclaimed that these cytokines are in peak level in the blood of psychiatric patients. Therefore, it is very much logical to suspect that these cytokine activation might underlie interplays between microglia and monocytes. Diverse discoveries imply that mild peripheral inflammation, which bestows to the pathogenesis of psychiatric disease-related events, including fatigue, may instigate microglial activation through neuronal networking. In addition to that, the symbioses between microglia and neuronal networks inflect myeloid cell proliferation through the autonomic nervous system (Spiegel., et al. 2008).
This work focus to identify and characterize novel targets that are potentially involved in the pathophysiology of psychiatric disorders. Congruous Microglia and monocytes have similar functions, surface markers, and gene expression profiles. Both cell types manumit pro-inflammatory cytokines when switched on in response to stimuli in the brain under various pathological conditions. Agglomerating data also betoken interactions between monocytes and microglia. New strategies can be expounded by doing Research into these interactions that may lead to the pathogenesis of psychiatric diseases. These interactions and chemistries can be used as peripheral biomarkers that echo the pathological conditions in the brain, conjunction with microglial activation related to the headway or Inflection of disease.
Conflict of Interest Statement
The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
  1. Theodoropoulou S., et al. “Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients”. Schizophrenia Research 47.1 (2001): 13–25.
  2. Drexhage RC., et al.  “The activation of monocyte and T cell networks in patients with bipolar disorder”. Brain, Behavior, and Immunity 25.6 (2011): 1206–1213.
  3. Padmos RC., et al. “A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes”. Archives of General Psychiatry 65.4 (2008): 395–407.
  4. Beumer W., et al. “The immune theory of psychiatric diseases: a key role for activated microglia and circulating monocytes”. Journal of Leukocyte Biology 92.5 (2012): 959–975.
  5. Shechter R and Schwartz M. “Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer ’if’ but ’how’”. The Journal of Pathology 229.2 (2013): 332–346.
  6. Prinz M and Priller J. “Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease”. Nature Reviews Neuroscience 15.5 (2014): 300–312.
  7. Schmitz G., et al. “Are circulating monocytes as microglia orthologues appropriate biomarker targets for neuronal diseases?”  Central Nervous System Agents in Medicinal Chemistry 9.4 (2009): 307–330.
  8. Radewicz K., et al. “Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics”. Journal of Neuropathology & Experimental Neurology 59.2    (2000): 137–150.
  9. Fillman SG., et al. “Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia”. Molecular Psychiatry 18.2 (2013): 206–214.
  10. Hercher C., et al. “Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder”. Journal of Psychiatry & Neuroscience 39.6 (2014): 376–385.
  11. Tang, B., et al. “Differential age- and disease-related effects on the expression of genes related to the arachidonic acid signaling pathway in schizophrenia”. Psychiatry Research 196 (2012): 201–206.
  12. Torres-Platas., et al. “Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides”. Brain, Behavior, and Immunity 42 (2014): 50–59.
  13. Ginhoux F., et al. “Fate mapping analysis reveals that adult microglia derive from primitive macrophages”. Science 330.6005 (2010): 841–845.
  14. Schulz C., et al. “A lineage of myeloid cells independent of Myb and hematopoietic stem cells”. Science 336.6077 (2012): 86–90.
  15. Kierdorf K., et al. “Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways”. Nature Neuroscience 16.3 (2013): 273–280.
  16. Goldmann T., et al. “A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation”. Nature Neuroscience 16 (2013): 1618–1626.
  17. Parkhurst CN., et al. “Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor”. Cell 155.7 (2013): 1596–1609.
  18. Yona S., et al. “Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis”. Immunity 38.1 (2013): 79–91.
  19. Barger SW and Basile AS. “Activation of microglia by secreted amyloid precursor protein evokes release of glutamate by cystine exchange and attenuates synaptic function”. Journal of Neurochemistry 76.3 (2001): 846–854.
  20. Takaki J., et al. “L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the ‘collusion’hypothesis for increased extracellular L-glutamate concentration in neuroinflammation”. Journal of Neuroinflammation 9 (2012): 275.
  21. Réus GZ., et al. “The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders”. Neuroscience 300 (2015): 141–154.
  22. Schmitz G and Grandl M. “Role of redox regulation and lipid rafts in macrophages during Ox-LDL-mediated foam cell formation”. Antioxidants & Redox Signaling 9.9 (2007): 1499–1518.
  23. Gordon S and Taylor PR. “Monocyte and macrophage heterogeneity”. Nature Reviews Immunology 5.12 (2005): 953–964.
  24. Lutter D., et al. “Analyzing M-CSF dependent monocyte/macrophage differentiation: expression modes and meta-modes derived from an independent component analysis”. BMC Bioinformatics 9 (2008): 100.
  25. Simard AR., et al. “Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease”. Neuron 49.4 (2006): 489–502.
  26. Mildner A., et al. “Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer’s disease”. The Journal of Neuroscience 31.31 (2011): 11159–11171.
  27. Jes Paul., et al. “Spinal Cord Regeneration and Functional Recovery: Neurotransmitter’s Combination and Bone Marrow Cells Supplementation”. Current Science 25 (2009): 546-549.
  28. Banks WA and Erickson MA. “The blood-brain barrier and immune function and dysfunction”. Neurobiology of Disease 37.1 (2010): 26–32.
  29. Spiegel A., et al. “Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment”. Cell Stem Cell 3.5 (2008): 484–492.
Citation: Jes Paul. “Discrepancy in Microglia and Peripheral Monocytic Cells, a Scope in the Pathophysiology of Psychiatric Maladies”. Current Opinions in Neurological Science 2.4 (2018): 506-510.
Copyright: © 2018 Jes Paul. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.