Changes in purinergic signaling after cerebral injury -- involvement of glutamatergic mechanisms?

Full Abstract

Extracellular purines act as neuromodulators on transmitter release and may exert toxic effects at higher concentrations. In microdialysis studies, endogenous ATP facilitated the extracellular concentration of glutamate in the nucleus accumbens (NAc) of rats. Additionally, P2 receptors are involved in astrogliosis in vivo after a stab wound injury in the same region, suggesting that these receptors, preferentially the metabotropic P2Y(1) receptor subtype, mediate also trophic responses. Two sets of experimental findings support the involvement of purinergic and glutamatergic mechanisms in the response of brain to mechanical damage. First, in the present studies, the initial time course of extracellular ATP and glutamate was analyzed after a mechanical injury. The concentration of ATP in microdialysates was elevated only in the first 15-min sample whereas glutamate returned to a basal concentration not before a 90-min period had elapsed. We suggest, that the acute injury-evoked stimulation of P2 receptors contributes to glutamate-mediated excitotoxicity. Second, the expression of P2Y(1) receptors and their possible relation to glutamatergic structures, identified by neuronal vesicular glutamate transporters (VGLUTs), were elucidated in non-treated and mechanically injured animals after 4 days. The number of P2Y(1)-positive cells was significantly increased after injury. Furthermore, P2Y(1) receptor-labeled cells do not exhibit immunoreactivity for VGLUT1 and VGLUT2 without and after injury. However, after injury, a co-expression of the P2Y(1) receptor on VGLUT3-immunopositive cells in the NAc was observed. No VGLUT1-, 2- and 3-immunoreactivity was found on P2Y(1)-positive glial fibrillary acidic protein-immunopositive astrocytes at both conditions. Our data suggest that the expression of P2Y(1) receptors at neurons and astrocytes is modulated in response to cerebral injury. It can be assumed, that the enhanced sensitivity of neurons to purinergic signaling may be related directly or indirectly to changes of the glutamatergic transmission.

Author information

Author/s: Franke, Heike (H); Grummich, Benjamin (B); Härtig, Wolfgang (W); Grosche, Jens (J); Regenthal, Ralf (R); Edwards, Robert H (RH); Illes, Peter (P); Krügel, Ute (U);

Affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (Int J Dev Neurosci), published in England. (Language: eng)

Reference: -2006 Apr-May; vol 24 (issue 2-3) : pp 123-32

Dates: Created 2006/02/28; Completed 2006/05/25; Revised 2006/11/15;

PMID: 16387466, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adenosine Triphosphate - metabolism
Analysis of Variance
Animals
Brain Injuries - metabolism
Chromatography, High Pressure Liquid - methods
Electrochemistry - methods
Fluorescent Antibody Technique - methods
Glial Fibrillary Acidic Protein - metabolism
Glutamic Acid - metabolism
Immunohistochemistry - methods
Male

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Glial Fibrillary Acidic Protein (0) ; Receptors, Purinergic P2 (0) ; Vesicular Glutamate Transport Protein 1 (0) ; Vesicular Glutamate Transport Protein 2 (0) ; purinoceptor P2Y1 (0) ; Adenosine Triphosphate (56-65-5) ; Glutamic Acid (56-86-0)

These are the most related articles currently in our database: