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Neuroinflammation is associated with changes in glial mGluR5 expression and the development of neonatal excitotoxic lesions

Drouin-Ouellet, Janelle LU ; Brownell, Anna-Liisa; Saint-Pierre, Martine; Fasano, Caroline; Emond, Vincent; Trudeau, Louis-Eric; Lévesque, Daniel and Cicchetti, Francesca (2011) In GLIA 59(2). p.99-188
Abstract

It has been hypothesized that neuroinflammation triggered during brain development can alter brain functions later in life. We investigated the contribution of inflammation to the alteration of normal brain circuitries in the context of neuroexcitotoxicity following neonatal ventral hippocampal lesions in rats with ibotenic acid, an NMDA glutamate receptor agonist. Excitotoxic ibotenic acid lesions led to a significant and persistent astrogliosis and microglial activation, associated with the production of inflammatory mediators. This response was accompanied by a significant increase in metabotropic glutamate receptor type 5 (mGluR5) expression within two distinct neuroinflammatory cell types; astrocytes and microglia. The... (More)

It has been hypothesized that neuroinflammation triggered during brain development can alter brain functions later in life. We investigated the contribution of inflammation to the alteration of normal brain circuitries in the context of neuroexcitotoxicity following neonatal ventral hippocampal lesions in rats with ibotenic acid, an NMDA glutamate receptor agonist. Excitotoxic ibotenic acid lesions led to a significant and persistent astrogliosis and microglial activation, associated with the production of inflammatory mediators. This response was accompanied by a significant increase in metabotropic glutamate receptor type 5 (mGluR5) expression within two distinct neuroinflammatory cell types; astrocytes and microglia. The participation of inflammation to the neurotoxin-induced lesion was further supported by the prevention of hippocampal neuronal loss, glial mGluR5 expression and some of the behavioral perturbations associated to the excitotoxic lesion by concurrent anti-inflammatory treatment with minocycline. These results indicate that neuroinflammation significantly contributes to long-lasting excitotoxic effects of the neurotoxin and to some behavioral phenotypes associated with this model. Thus, the control of the inflammatory response may prevent the deleterious effects of excitotoxic processes that are triggered during brain development, limiting the risk to develop some of the behavioral manifestations related to these processes in adulthood.

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@article{b956a6ee-6ac4-423c-bc51-05f0d420892a,
  abstract     = {<p>It has been hypothesized that neuroinflammation triggered during brain development can alter brain functions later in life. We investigated the contribution of inflammation to the alteration of normal brain circuitries in the context of neuroexcitotoxicity following neonatal ventral hippocampal lesions in rats with ibotenic acid, an NMDA glutamate receptor agonist. Excitotoxic ibotenic acid lesions led to a significant and persistent astrogliosis and microglial activation, associated with the production of inflammatory mediators. This response was accompanied by a significant increase in metabotropic glutamate receptor type 5 (mGluR5) expression within two distinct neuroinflammatory cell types; astrocytes and microglia. The participation of inflammation to the neurotoxin-induced lesion was further supported by the prevention of hippocampal neuronal loss, glial mGluR5 expression and some of the behavioral perturbations associated to the excitotoxic lesion by concurrent anti-inflammatory treatment with minocycline. These results indicate that neuroinflammation significantly contributes to long-lasting excitotoxic effects of the neurotoxin and to some behavioral phenotypes associated with this model. Thus, the control of the inflammatory response may prevent the deleterious effects of excitotoxic processes that are triggered during brain development, limiting the risk to develop some of the behavioral manifestations related to these processes in adulthood.</p>},
  author       = {Drouin-Ouellet, Janelle and Brownell, Anna-Liisa and Saint-Pierre, Martine and Fasano, Caroline and Emond, Vincent and Trudeau, Louis-Eric and Lévesque, Daniel and Cicchetti, Francesca},
  issn         = {1098-1136},
  keyword      = {Amphetamine,Animals,Animals, Newborn,Anti-Inflammatory Agents,Behavior, Animal,Cells, Cultured,Central Nervous System Stimulants,Cytokines,Disease Models, Animal,Encephalitis,Enzyme-Linked Immunosorbent Assay,Female,Gene Expression Regulation, Developmental,Hippocampus,Ibotenic Acid,Interpersonal Relations,Isoquinolines,Male,Maze Learning,Microtubule-Associated Proteins,Minocycline,Motor Activity,Neuroglia,Neurons,Neurotoxicity Syndromes,Phosphopyruvate Hydratase,Positron-Emission Tomography,Pregnancy,Radioligand Assay,Rats,Receptor, Metabotropic Glutamate 5,Receptors, Metabotropic Glutamate,Tritium,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {99--188},
  publisher    = {John Wiley & Sons},
  series       = {GLIA},
  title        = {Neuroinflammation is associated with changes in glial mGluR5 expression and the development of neonatal excitotoxic lesions},
  url          = {http://dx.doi.org/10.1002/glia.21086},
  volume       = {59},
  year         = {2011},
}