The role of macrophages in models of neurological and psychiatric disorder

Perry, V.H.

doi:10.1017/s0033291700038009

Cited by 11 publications

(7 citation statements)

References 38 publications

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“…In susceptible individuals, if this state is not alleviated, it may become chronic, potentially leading to autism. As noted earlier, the stress-induced dysfunctional mitochondria may cause an immune response, e.g., abnormal macrophage excitation, penetration into the brain, activation of microglia and further brain stimulation via inappropriate release of chemical messengers, simply by having a hypoxic event, which the stressor initially causes [12,13,17,27]. Predicted entry points, e.g., choroid plexus, would provide widespread access to the privileged compartment and explain the diverse symptomology of autism.…”

Section: Consolidationmentioning

confidence: 99%

Mitochondria, Microbiome and Their Potential Psychiatric Modulation

Snyder¹,

Kream²,

Ptáček³

et al. 2015

Autism Open Access

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Pervasive developmental disorders, or autism spectrum disorders, are multifaceted and have a high rate of occurrence. Additionally, the origin of Autism appears to be multidimensional and largely unknown. Thus, it would appear novel approaches and concepts are needed in this area of scientific endeavor. In this regard, microbial cells harbored within the human gut and elsewhere are being studied to understand their multi-functional properties and their ability to affect physiological activities in their "host" organism. The communities of approximately 10 trillion microbial cells that live within the gut are involved in functions such as metabolism, nutrition and immune regulation. We and others surmise this microbiota can contribute to disruption of normal activities, causing harmful pathologies such as gastrointestinal complications, obesity, and diabetes and autism. They have the ability to trigger inappropriate immune activation, especially macrophages, which can travel from the gut and penetrate the blood brain barrier and communicate inappropriately with neural cells, altering behavior. Normally these immune cells can enter the brain and become microglia. However, being abnormally stimulated, many more can enter the brain, awakening the sentinel microglia and establishing a proinflammatory state, inducing hypoxia (altering mitochondrial performance). Thus, the microbiome has the potential to extend its influence into the brain, suggesting this may also take place within the parameters of normal activity. In part, the behavioral outcome of such an inappropriate invasion would depend on the region(s) penetrated, manifesting itself with a multidimensional behavioral profile such as occurs in autism.

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Section: Consolidationmentioning

confidence: 99%

Mitochondria, Microbiome and Their Potential Psychiatric Modulation

Snyder¹,

Kream²,

Ptáček³

et al. 2015

Autism Open Access

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“…Today, the special status of microglia is known to be based on its mesodermal origin, a concept that, after many years of debate, now appears to have become firmly established (see refs. [2][3][4]. It is derived from cells of the immune system which, in the process of establishing residency in the developing nervous system as intrinsic immunoeffector cells, undergo certain structural and biochemical transformations.…”

mentioning

confidence: 99%

“…In response to trauma, such as experimental interference with normal neuron-glia interaction, microglia regains some of its inherent immunoregulatory attributes; the cells change shape and engage in migratory and phagocytotic activity (2,3,5).…”

mentioning

confidence: 99%

Microglia in invertebrate ganglia.

Sonetti

Ottaviani

Bianchi

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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The results of this study lend strong support to the concept of the existence in insects and molluscs of a distinctive class of neuroglial cells comparable to vertebrate microglia. The evidence presented is as valid as that used in reference to the separate status of vertebrate microglia-i.e., the demonstration of a close structural and functional relationship of these cells with cells of the immune system. As in vertebrates, the excision of gala from three invertebrate species (the molluscs Planorbarus corneas and Mytilus edulis and the insect Leucophaea maderae) and their maintenance in incubation media led to an exodus of small cells and their accumulation in the culture dish. During this process, they underwent conformational changes from stellate to rounded, and then to more or less ameboid, comparable to those indicative of the process of activation in the animals' immunocytes. Functional characteristics which these translocated microglia-like cells share with immunocytes are motility, phagocytotic activity, and adherence to the culture dish. Furthermore, the two cells have certain biochemical features in common-e.g., the presence of certain cytokines and (at least in Planorbarius) that of corticotropin. An additional phenomenon of particular interest for the classification of mirogHal elements is their response to morphine. At 10-6 M, this drug decreases not only the number of cells emerging from the excised ganglia but also the degree of their transformation to the "active" ameboid form. This dose-dependent and naloxone-sensitive effect of morphine on microglial cells parallels that on activated immunocyts of the same species. Corre

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“…By functional criteria, noted earlier, activated or polarized macrophages represent a potent immune cell type with the potential to secrete numerous neuroactive signal molecules that permit free penetration of the vertebrate the blood-brain barrier. Operationally, macrophages appear to be sentinels of the immune and nervous systems and may exert the same type of surveillance in other systems as well [14]. Invertebrate ganglia contain microglia and macrophage-like cells in their open ganglionic nervous system [33].…”

Section: Additional Functional Commonalitiesmentioning

confidence: 99%

“…As discussed in depth below, the intrinsic, state-dependent, plasticity of microglia has provoked considerable empirical investigation into their functional/regulatory roles in mediating innate immune surveillance and neural protection within the CNS. When dysregulated, it appears that aberrant microglial activities represent significant contributory factors in the etiology and persistence of major neurological, degenerative, and psychiatric disorders [11,12,14,15].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary Perspective on Microglial/Neuronal Coupling with Special Relevance to Psychiatric Illnesses

Stefano¹,

Kream²

2015

J Psychiatry

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Journal of Psychiatry AbstractMicroglia have selectively evolved as a morphologically and chemically distinct class of immuno-competent CNS resident cells with potent bidirectional signaling capabilities linked to induction of a macrophage-like phenotype following metabolic, microbiological, or viral insults. It has been empirically determined that a conserved set of shared chemical messengers connects a communication network mediating reciprocal exchange of regulatory information between immune, central nervous, and neuroendocrine systems. From an evolutionary perspective, the pluripotent neuro-protective capabilities of invertebrate microglia have been extended and amplified in classes of mammalian microglia. The state-dependent plasticity of microglia has provoked considerable empirical investigation into their functional/regulatory roles in mediating innate immune surveillance and neural protection within the CNS. Upon pathophysiological dysregulation, aberrant microglial activities may provide significant contributory factors in the etiology and persistence of major neurological, degenerative, and psychiatric disorders. Within this context, invertebrate microglia appear to represent highly appropriate model systems to investigate underlying cellular and molecular mechanisms involved in higher order neuroimmune regulation of multiple CNS activities by mammalian microglia.

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The role of macrophages in models of neurological and psychiatric disorder

Cited by 11 publications

References 38 publications

Mitochondria, Microbiome and Their Potential Psychiatric Modulation

Mitochondria, Microbiome and Their Potential Psychiatric Modulation

Microglia in invertebrate ganglia.

Evolutionary Perspective on Microglial/Neuronal Coupling with Special Relevance to Psychiatric Illnesses

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