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Intracerebroventricular administration of quinolinic acid induces a selective decrease of inositol(1,4,5)-trisphosphate receptor in rat brain.

Authors: Haug, LS  Ostvold, AC  Torgner, I  Roberg, B  Dvorakova, L  St'astny, F  Walaas, SI 
Citation: Haug LS, etal., Neurochem Int. 1998 Aug;33(2):109-19.
Pubmed: (View Article at PubMed) PMID:9761455

[3H]inositol(1,4,5)-trisphosphate (IP3) binding studies have shown decreased [3H]IP3 binding to brain tissue in several neurodegenerative diseases, including Alzheimer's and Huntington's diseases. In addition, previous results obtained from brains of Alzheimer patients indicated a reduction of IP3-receptor protein correlated to neuronal loss. The neurotoxic effect of the glutamate receptor agonist quinolinic acid (QUIN) was therefore examined with respect to the level of IP3-receptor immunoreactivity in rat brain. Neuronal lesions were estimated with antibodies to marker proteins for striatal medium-sized spiny neurons (dopamine- and cyclic AMP-regulated phosphoprotein, Mr 32,000; DARPP-32), synaptic vesicles (synaptophysin), mitochondria (phosphate-activated glutaminase; PAG) and glial cells (glial fibrillary acidic protein; GFAP). Injection of QUIN into rat neostriatum induced a massive loss of striatal medium-sized spiny neurons, and led to a comparable loss of IP3-receptor and PAG immunoreactivity, suggesting a neuronal localisation of both these proteins. In an effort to induce less pronounced excitotoxic damage, intracerebroventricular infusion of QUIN was performed. Following this lesion, the neostriatum showed a negligible loss of DARPP-32 immunoreactivity (-11+/-5%), but contained only 43+/-3% of IP3-receptor immunoreactivity levels compared to controls. In the hippocampus, cerebellum and entorhinal cortex, the IP3-receptor loss was less pronounced. The decrease in the level of IP3-receptor immunoreactivity appears to be selective with respect to the other proteins studied, and the IP3-receptor thus shows extreme sensitivity to QUIN neurotoxicity in the neostriatum.


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RGD Object Information
RGD ID: 6483009
Created: 2012-05-09
Species: All species
Last Modified: 2012-05-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.