Glutamate Uptake is Reduced in Prefrontal Cortex in Huntington’s Disease
Huntington’s disease (HD) is caused by a CAG repeat expansion in the HD gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CA...
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| Veröffentlicht in: | Neurochemical research 2008-02, Vol.33 (2), p.232-237 |
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| creator | Hassel, Bjørnar Tessler, Shoshi Faull, Richard L. M. Emson, Piers C. |
| description | Huntington’s disease (HD) is caused by a CAG repeat expansion in the
HD
gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the
HD
gene. In seven HD patients with moderate CAG expansions (40–52), repeat expansion and HD grade at autopsy were strongly correlated (
r
= 0.88,
p
= 0.0002). Uptake of [
3
H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (
r
= −0.82,
p
= 0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD. |
| doi_str_mv | 10.1007/s11064-007-9463-1 |
| format | Article |
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HD
gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the
HD
gene. In seven HD patients with moderate CAG expansions (40–52), repeat expansion and HD grade at autopsy were strongly correlated (
r
= 0.88,
p
= 0.0002). Uptake of [
3
H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (
r
= −0.82,
p
= 0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD.</description><identifier>ISSN: 0364-3190</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-007-9463-1</identifier><identifier>PMID: 17726644</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Astrocytes - pathology ; Biochemistry ; Biological Transport ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Glutamic Acid - metabolism ; Humans ; Huntington Disease - metabolism ; Neurochemistry ; Neurology ; Neurosciences ; Original Paper ; Prefrontal Cortex - metabolism ; Prefrontal Cortex - pathology ; Trinucleotide Repeats</subject><ispartof>Neurochemical research, 2008-02, Vol.33 (2), p.232-237</ispartof><rights>Springer Science+Business Media, LLC 2007</rights><rights>Springer Science+Business Media, LLC 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-8df9d39d172eb5fe750890d2b202e7420f77cdc65a534f9d29a23541809a32bc3</citedby><cites>FETCH-LOGICAL-c466t-8df9d39d172eb5fe750890d2b202e7420f77cdc65a534f9d29a23541809a32bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11064-007-9463-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11064-007-9463-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17726644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hassel, Bjørnar</creatorcontrib><creatorcontrib>Tessler, Shoshi</creatorcontrib><creatorcontrib>Faull, Richard L. M.</creatorcontrib><creatorcontrib>Emson, Piers C.</creatorcontrib><title>Glutamate Uptake is Reduced in Prefrontal Cortex in Huntington’s Disease</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><addtitle>Neurochem Res</addtitle><description>Huntington’s disease (HD) is caused by a CAG repeat expansion in the
HD
gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the
HD
gene. In seven HD patients with moderate CAG expansions (40–52), repeat expansion and HD grade at autopsy were strongly correlated (
r
= 0.88,
p
= 0.0002). Uptake of [
3
H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (
r
= −0.82,
p
= 0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD.</description><subject>Astrocytes - pathology</subject><subject>Biochemistry</subject><subject>Biological Transport</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Glutamic Acid - metabolism</subject><subject>Humans</subject><subject>Huntington Disease - metabolism</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Original Paper</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Prefrontal Cortex - pathology</subject><subject>Trinucleotide Repeats</subject><issn>0364-3190</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc9q3DAQxkVpaLZJHqCXYnrozcnMSJZWx7Jt84dAS2nOQmuPg1OvvZVkaG55jbxen6QyuxAohJw0aH7fN8x8QrxDOEUAcxYRQasyl6VVWpb4SiywMrLUFuRrsQCZuxItHIq3Md4BZBXhG3GIxpDWSi3E1Xk_Jb_xiYubbfK_uOhi8YObqeam6Ibie-A2jEPyfbEaQ-I_8-fFNKRuuE3j8PfhMRafu8g-8rE4aH0f-WT_Hombr19-ri7K62_nl6tP12WttE7lsmltI22DhnhdtWwqWFpoaE1AbBRBa0zd1LrylVQZJetJVgqXYL2kdS2PxMed7zaMvyeOyW26WHPf-4HHKToDJA2hehFEq4xWpDP44T_wbpzCkJdwRLgkC3Z2wx1UhzHGfBa3Dd3Gh3uH4OY43C4ON5dzHA6z5v3eeFpvuHlS7O-fAdoBMbeGWw5Pk593_QcdgJQ6</recordid><startdate>20080201</startdate><enddate>20080201</enddate><creator>Hassel, Bjørnar</creator><creator>Tessler, Shoshi</creator><creator>Faull, Richard L. 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M. ; Emson, Piers C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-8df9d39d172eb5fe750890d2b202e7420f77cdc65a534f9d29a23541809a32bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Astrocytes - pathology</topic><topic>Biochemistry</topic><topic>Biological Transport</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Glutamic Acid - metabolism</topic><topic>Humans</topic><topic>Huntington Disease - metabolism</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Original Paper</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Prefrontal Cortex - pathology</topic><topic>Trinucleotide Repeats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hassel, Bjørnar</creatorcontrib><creatorcontrib>Tessler, Shoshi</creatorcontrib><creatorcontrib>Faull, Richard L. 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M.</au><au>Emson, Piers C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glutamate Uptake is Reduced in Prefrontal Cortex in Huntington’s Disease</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2008-02-01</date><risdate>2008</risdate><volume>33</volume><issue>2</issue><spage>232</spage><epage>237</epage><pages>232-237</pages><issn>0364-3190</issn><eissn>1573-6903</eissn><abstract>Huntington’s disease (HD) is caused by a CAG repeat expansion in the
HD
gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the
HD
gene. In seven HD patients with moderate CAG expansions (40–52), repeat expansion and HD grade at autopsy were strongly correlated (
r
= 0.88,
p
= 0.0002). Uptake of [
3
H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (
r
= −0.82,
p
= 0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>17726644</pmid><doi>10.1007/s11064-007-9463-1</doi><tpages>6</tpages></addata></record> |
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| ispartof | Neurochemical research, 2008-02, Vol.33 (2), p.232-237 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Astrocytes - pathology Biochemistry Biological Transport Biomedical and Life Sciences Biomedicine Cell Biology Glutamic Acid - metabolism Humans Huntington Disease - metabolism Neurochemistry Neurology Neurosciences Original Paper Prefrontal Cortex - metabolism Prefrontal Cortex - pathology Trinucleotide Repeats |
| title | Glutamate Uptake is Reduced in Prefrontal Cortex in Huntington’s Disease |
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