Opiate signaling regulates microglia activities in the invertebrate nervous system

Sonetti, Dario; Ottaviani, Enzo; Stefano, George B.

doi:10.1016/s0306-3623(96)00523-x

Cited by 32 publications

(18 citation statements)

References 37 publications

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“…In this report, we found that only one set of -specific primers used in the PCR (from map position 896-1336) yielded a specific PCR product (32). This segment of the cDNA encodes the third extracellular loop of the receptor that is important for agonist selectivity (33,34).…”

Section: Discussionmentioning

confidence: 85%

A Functionally Coupled μ3-Like Opiate Receptor/Nitric Oxide Regulatory Pathway in Human Multi-Lineage Progenitor Cells

Cadet

Mantione

Zhu

et al. 2007

The Journal of Immunology

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Ongoing studies from our group support the existence and biological importance of a distinct cellular signaling pathway involving endogenously synthesized, chemically authentic, l-morphine, its cognate μ3 opiate receptor subtype, and constitutive NO synthase. Based on prior studies indicating evolutionary conservation and adaptation of morphinergic/NO-coupled signaling to mediate autocrine/paracrine control of cellular functions, our goal was to determine whether a functionally competent μ3 opiate receptor/NO-coupled regulatory pathway exists in human multilineage progenitor cells (MLPC) prepared from umbilical cord blood. Real-time PCR analysis indicated significant expression of μ3 opiate receptor-encoding RNA by undifferentiated human MLPC, in the absence of traditional μ1 opioid receptor-encoding RNA expression. Unpredictably, confirmatory RT-PCR analyses indicated cellular expression of a splice variant of the previously characterized μ3 opiate receptor-encoding mRNA. Pharmacological analyses provided critical validating evidence of functional μ3-like opiate receptor/NO-coupled signaling within primary cultures of undifferentiated human MLPC via morphine-evoke real-time release of NO. Control analyses indicated that morphine-stimulated NO release was markedly inhibited by prior treatment with the opiate antagonist l-naloxone or the constitutive NO synthase inhibitor N(G)-nitro-l-arginine methyl ester and unresponsive to stimulation by the opioid peptide methionine enkephalin. Complementary microarray analysis demonstrated that traditional μ1, δ, and κ opioid receptor gene expression is not detected in both undifferentiated and differentiated MLPC. Chemical differentiation of MLPC into neuronal progenitor cells effected significant phenotypic expression of a variety of neurally-associated genes. Our data provide compelling evidence in support of both the evolutionary primacy and primordial regulatory role of μ3-like opiate receptor/NO signaling in embryogenesis.

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Section: Discussionmentioning

confidence: 85%

A Functionally Coupled μ3-Like Opiate Receptor/Nitric Oxide Regulatory Pathway in Human Multi-Lineage Progenitor Cells

Cadet

Mantione

Zhu

et al. 2007

The Journal of Immunology

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“…Traumatic injury triggers proliferative response in microglial cells from Planorbarius corneus (712); activation of microglia was associated with expression of inducible NOS (iNOS) (711). Evidence also exists that opiate signaling regulates microglial activities in this mollusc (848).…”

Section: Evolutionary Origins Of Microgliamentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,134

2,981

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Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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“…In earlier reports, invertebrate immuno-competent glial cells have been demonstrated to possess similar properties as previously described for mammalian microglia including a shared set of chemical messengers such as interleukins and opioid peptides [61][62][63][64]. These morphological and biochemical similarities suggest an evolutionarily driven functional convergence of immuno-competent glial cells [62][63][64]. In this regard, our group and others have demonstrated compelling anatomical and biochemical linkages between invertebrate immunocytes/microglia and mammalian monocytic/microglial/macrophage lineages that include functional utilization of a shared set of chemical messengers [27,43,44,51,[65][66][67].…”

Section: Evolutionary Origin Of Microglial/neuronal Couplingmentioning

confidence: 66%

“…For example, one of the activities linked to invertebrate glia is functionally associated with the blood-brain barrier integrity of insects, as well as maintenance and repair of invertebrate nerve cells [61]. In earlier reports, invertebrate immuno-competent glial cells have been demonstrated to possess similar properties as previously described for mammalian microglia including a shared set of chemical messengers such as interleukins and opioid peptides [61][62][63][64]. These morphological and biochemical similarities suggest an evolutionarily driven functional convergence of immuno-competent glial cells [62][63][64].…”

Section: Evolutionary Origin Of Microglial/neuronal Couplingmentioning

confidence: 83%

“…As documented by video time lapse microscopy [62,74], this phenomenon is visualized by stationary microglia becoming amoeboid, macrophage-like, and mobile following traumatic stimuli in invertebrate ganglia [62][63][64]75]. 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.…”

Section: Additional Functional Commonalitiesmentioning

confidence: 99%

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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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Opiate signaling regulates microglia activities in the invertebrate nervous system

Cited by 32 publications

References 37 publications

A Functionally Coupled μ3-Like Opiate Receptor/Nitric Oxide Regulatory Pathway in Human Multi-Lineage Progenitor Cells

A Functionally Coupled μ3-Like Opiate Receptor/Nitric Oxide Regulatory Pathway in Human Multi-Lineage Progenitor Cells

Physiology of Microglia

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

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