RGD Reference Report - Overactivation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion. - Rat Genome Database
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Overactivation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion.

Authors: Xu, Cheng-Shi  Liu, An-Chun  Chen, Juan  Pan, Zhi-Yong  Wan, Qi  Li, Zhi-Qiang  Wang, Ze-Fen 
Citation: Xu CS, etal., J Neurochem. 2015 Aug;134(3):566-77. doi: 10.1111/jnc.13134. Epub 2015 Jun 4.
RGD ID: 13800913
Pubmed: (View Article at PubMed) PMID:25903928
DOI: Full-text: DOI:10.1111/jnc.13134

Middle cerebral artery occlusion (MCAO) induces secondary damages in the hippocampus that is remote from primary ischemic regions. Tau hyperphosphorylation is an important risk for neurodegenerative diseases. Increased tau phosphorylation has been identified in ischemic cortex, but little is known regarding the changes in the hippocampus. We showed that unilateral transient MCAO induced accumulation of hyperphosphorylated tau and concurrent dephosphorylation of glycogen synthase kinase-3ß at Ser 9 in the ipsilateral hippocampus. These MCAO-induced changes were not reproduced when glutamatergic inputs from the entorhinal cortex to the hippocampus were transected; however, the changes were mimicked by intrahippocampal N-methyl-d-aspartate (NMDA) administration. Inhibition of NMDA receptor (NMDAR) subunit NR2B, but not NR2A activity in the hippocampus attenuated the accumulation of hyperphosphorylated tau and spatial cognitive impairment in MCAO rats. Together, our data suggest that overactivation of NR2B-containing NMDARs through entorhinal-hippocampal connection plays an important role in the accumulation of hyperphosphorylated tau in the hippocampus following MCAO. Glycogen synthase kinase-3ß is an important protein kinase involved in NMDARs-mediated tau hyperphosphorylation. This study indicates that early inhibition of NR2B-containing NMDARs may represent a potential strategy to prevent or delay the occurrence of post-stroke dementia. Middle cerebral artery occlusion induces secondary damage in the hippocampus that is remote from primary ischemic regions. We propose that excessive activation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiated the accumulation of hyperphosphorylated tau in the hippocampus, which subsequently induced cognitive deficit. This study provides new insights into the prospects of NR2B inhibition in stoke therapy.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mapt  (microtubule-associated protein tau)

Genes (Mus musculus)
Mapt  (microtubule-associated protein tau)

Genes (Homo sapiens)
MAPT  (microtubule associated protein tau)


Additional Information