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The chemokine CCL2 modulates Ca2+ dynamics and electrophysiological properties of cultured cerebellar Purkinje neurons

Academic Article
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Overview

authors

  • van Gassen, K. L. I.
  • Netzeband, J. G.
  • de Graan, P. N. E.
  • Gruol, Donna

publication date

  • June 2005

journal

  • European Journal of Neuroscience  Journal

abstract

  • The chemokine CCL2 is produced at high levels in the central nervous system (CNS) during infection, injury, neuroinflammation and other pathological conditions. Cells of the CNS including neurons and glia express receptors for CCL2 and these receptors may contribute to a signaling system through which pathologic conditions in the CNS are communicated. However, our understanding of the consequences of activation of chemokine signaling in the CNS is limited, especially for neurons. In many cell types, chemokine signaling alters intracellular Ca(2+) dynamics. Therefore, we investigated the potential involvement of this mechanism in neuronal signaling activated by CCL2. In addition, we examined the effects of CCL2 on neuronal excitability. The studies focused on the rat cerebellar Purkinje neuron, an identified CNS neuronal type reported to express both CCL2 and its receptor, CCR2. Immunohistochemical studies of Purkinje neurons in situ confirmed that they express CCR2 and CCL2. The effect of exogenous application on Purkinje neurons was studied in a cerebellar culture preparation. CCL2 was tested by micropressure or bath application, at high concentrations (13-100 nm) to simulate conditions during a pathologic state. Results show that Purkinje neurons express receptors for CCL2 and that activation of these receptors alters several neuronal properties. CCL2 increased resting Ca(2+) levels, enhanced the Ca(2+) response evoked by activation of metabotropic glutamate receptor 1 and depressed action potential generation in the cultured Purkinje neurons. Passive membrane properties were unaltered. These modulatory effects of CCL2 on neuronal properties are likely to contribute to the altered CNS function associated with CNS disease and injury.

subject areas

  • Action Potentials
  • Animals
  • Calcium
  • Calcium Signaling
  • Cell Membrane
  • Chemokine CCL2
  • Dose-Response Relationship, Drug
  • Immunohistochemistry
  • Neural Inhibition
  • Neuroimmunomodulation
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Purkinje Cells
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Metabotropic Glutamate
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Research

keywords

  • calcium signaling
  • inflammatory mediators
  • metabotropic glutamate receptor
  • neurodegenerative disorders
  • rat brain
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Identity

International Standard Serial Number (ISSN)

  • 0953-816X

Digital Object Identifier (DOI)

  • 10.1111/j.1460-9568.2005.04113.x

PubMed ID

  • 15978006
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Additional Document Info

start page

  • 2949

end page

  • 2957

volume

  • 21

issue

  • 11

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