Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function
Obstructive sleep apnea (OSA) is a frequent medical condition characterized by intermittent hypoxia (IH) during sleep, and is associated with neurodegenerative changes in several brain regions along with learning deficits. We hypothesized that aging rats exposed to IH during sleep would be particula...
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| Veröffentlicht in: | Journal of neurochemistry 2003-09, Vol.86 (6), p.1545-1552 |
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| container_title | Journal of neurochemistry |
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| creator | Gozal, David Row, Barry W. Kheirandish, Leila Liu, Rugao Guo, Shang Z. Qiang, Fan Brittian, Kenneth R. |
| description | Obstructive sleep apnea (OSA) is a frequent medical condition characterized by intermittent hypoxia (IH) during sleep, and is associated with neurodegenerative changes in several brain regions along with learning deficits. We hypothesized that aging rats exposed to IH during sleep would be particularly susceptible. Young (3–4 months) and aging (20–22 months) Sprague–Dawley rats were therefore exposed to either room air or IH for 14 days. Learning and memory was assessed with a standard place‐training version of the Morris water maze. Aging rats exposed to room air (RA) or IH displayed significant spatial learning impairments compared with similarly exposed young rats; furthermore, the decrements in performance between RA and IH were markedly greater in aging compared with young rats (p |
| doi_str_mv | 10.1046/j.1471-4159.2003.01973.x |
| format | Article |
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We hypothesized that aging rats exposed to IH during sleep would be particularly susceptible. Young (3–4 months) and aging (20–22 months) Sprague–Dawley rats were therefore exposed to either room air or IH for 14 days. Learning and memory was assessed with a standard place‐training version of the Morris water maze. Aging rats exposed to room air (RA) or IH displayed significant spatial learning impairments compared with similarly exposed young rats; furthermore, the decrements in performance between RA and IH were markedly greater in aging compared with young rats (p < 0.01), and coincided with the magnitude of IH‐induced decreases in cyclic AMP response element binding (CREB) phosphorylation. Furthermore, decreases in proteasomal activity occurred in both young and aging rats exposed to IH, but were substantially greater in the latter (p < 0.001). Neuronal apoptosis, as shown by cleaved caspase 3 expression, was particularly increased in aging rats exposed to IH (p < 0.01 versus young rats exposed to IH). Collectively, these findings indicate unique vulnerability of the aging rodent brain to IH, which is reflected at least in part, by the more prominent decreases in CREB phosphorylation and a marked inability of the ubiquitin‐proteasomal pathway to adequately clear degraded proteins.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2003.01973.x</identifier><identifier>PMID: 12950463</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>aging ; Aging - metabolism ; Animals ; Apoptosis ; Biological and medical sciences ; Caspase 3 ; Caspases - metabolism ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cysteine Endopeptidases - metabolism ; Hypoxia - physiopathology ; intermittent hypoxia ; Maze Learning ; Medical sciences ; Multienzyme Complexes - metabolism ; Nervous system involvement in other diseases. Miscellaneous ; Neurology ; Neurons - metabolism ; Neurons - pathology ; Phosphorylation ; proteasome ; Proteasome Endopeptidase Complex ; Rats ; Rats, Sprague-Dawley ; sleep apnea ; Sleep Apnea, Obstructive - physiopathology ; Spatial Behavior ; spatial learning</subject><ispartof>Journal of neurochemistry, 2003-09, Vol.86 (6), p.1545-1552</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4763-f30afa5e76f4a357b29ce2f3f87fb4808223fbc6cf2b2986e3211b14e78f66ef3</citedby><cites>FETCH-LOGICAL-c4763-f30afa5e76f4a357b29ce2f3f87fb4808223fbc6cf2b2986e3211b14e78f66ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2003.01973.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2003.01973.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15102020$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12950463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>Row, Barry W.</creatorcontrib><creatorcontrib>Kheirandish, Leila</creatorcontrib><creatorcontrib>Liu, Rugao</creatorcontrib><creatorcontrib>Guo, Shang Z.</creatorcontrib><creatorcontrib>Qiang, Fan</creatorcontrib><creatorcontrib>Brittian, Kenneth R.</creatorcontrib><title>Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Obstructive sleep apnea (OSA) is a frequent medical condition characterized by intermittent hypoxia (IH) during sleep, and is associated with neurodegenerative changes in several brain regions along with learning deficits. We hypothesized that aging rats exposed to IH during sleep would be particularly susceptible. Young (3–4 months) and aging (20–22 months) Sprague–Dawley rats were therefore exposed to either room air or IH for 14 days. Learning and memory was assessed with a standard place‐training version of the Morris water maze. Aging rats exposed to room air (RA) or IH displayed significant spatial learning impairments compared with similarly exposed young rats; furthermore, the decrements in performance between RA and IH were markedly greater in aging compared with young rats (p < 0.01), and coincided with the magnitude of IH‐induced decreases in cyclic AMP response element binding (CREB) phosphorylation. Furthermore, decreases in proteasomal activity occurred in both young and aging rats exposed to IH, but were substantially greater in the latter (p < 0.001). Neuronal apoptosis, as shown by cleaved caspase 3 expression, was particularly increased in aging rats exposed to IH (p < 0.01 versus young rats exposed to IH). Collectively, these findings indicate unique vulnerability of the aging rodent brain to IH, which is reflected at least in part, by the more prominent decreases in CREB phosphorylation and a marked inability of the ubiquitin‐proteasomal pathway to adequately clear degraded proteins.</description><subject>aging</subject><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cysteine Endopeptidases - metabolism</subject><subject>Hypoxia - physiopathology</subject><subject>intermittent hypoxia</subject><subject>Maze Learning</subject><subject>Medical sciences</subject><subject>Multienzyme Complexes - metabolism</subject><subject>Nervous system involvement in other diseases. Miscellaneous</subject><subject>Neurology</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Phosphorylation</subject><subject>proteasome</subject><subject>Proteasome Endopeptidase Complex</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>sleep apnea</subject><subject>Sleep Apnea, Obstructive - physiopathology</subject><subject>Spatial Behavior</subject><subject>spatial learning</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2OFCEUhYnROO3oKxg2urJKLlBQZeJi0vFnzEQ3uiYUAz10qqAsKO1-Ax9byu44Sw0LyLnfPfeSgxAGUgPh4vW-Bi6h4tB0NSWE1QQ6yerDA7T5W3iINoRQWjHC6QV6ktKeEBBcwGN0AbRrig_boF_XwcxWJ3uL05KMnbLv_eDzEeeIfch2Hn3ONmR8d5ziwesiYr3zYYdnndMbbO502Nm0ytMcc7GKox6wNtn_KDavcLDLHMMqTXHKMfmEdSjTJp19Ud0SChrDU_TI6SHZZ-f7En17_-7r9mN18-XD9fbqpjJcClY5RrTTjZXCcc0a2dPOWOqYa6XreUtaSpnrjTCOllIrLKMAPXArWyeEdewSvTz5lm2_LzZlNfry72HQwcYlKckEMMbpP0HoQHKQUMD2BJo5pjRbp6bZj3o-KiBqjUvt1ZqKWlNRa1zqT1zqUFqfn2cs_Whv7xvP-RTgxRnQyejBzToYn-65Bggtp3BvT9xPP9jjfy-gPn3eri_2G-JDs_M</recordid><startdate>200309</startdate><enddate>200309</enddate><creator>Gozal, David</creator><creator>Row, Barry W.</creator><creator>Kheirandish, Leila</creator><creator>Liu, Rugao</creator><creator>Guo, Shang Z.</creator><creator>Qiang, Fan</creator><creator>Brittian, Kenneth R.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>200309</creationdate><title>Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function</title><author>Gozal, David ; Row, Barry W. ; Kheirandish, Leila ; Liu, Rugao ; Guo, Shang Z. ; Qiang, Fan ; Brittian, Kenneth R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4763-f30afa5e76f4a357b29ce2f3f87fb4808223fbc6cf2b2986e3211b14e78f66ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>aging</topic><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cysteine Endopeptidases - metabolism</topic><topic>Hypoxia - physiopathology</topic><topic>intermittent hypoxia</topic><topic>Maze Learning</topic><topic>Medical sciences</topic><topic>Multienzyme Complexes - metabolism</topic><topic>Nervous system involvement in other diseases. Miscellaneous</topic><topic>Neurology</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Phosphorylation</topic><topic>proteasome</topic><topic>Proteasome Endopeptidase Complex</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>sleep apnea</topic><topic>Sleep Apnea, Obstructive - physiopathology</topic><topic>Spatial Behavior</topic><topic>spatial learning</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>Row, Barry W.</creatorcontrib><creatorcontrib>Kheirandish, Leila</creatorcontrib><creatorcontrib>Liu, Rugao</creatorcontrib><creatorcontrib>Guo, Shang Z.</creatorcontrib><creatorcontrib>Qiang, Fan</creatorcontrib><creatorcontrib>Brittian, Kenneth R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gozal, David</au><au>Row, Barry W.</au><au>Kheirandish, Leila</au><au>Liu, Rugao</au><au>Guo, Shang Z.</au><au>Qiang, Fan</au><au>Brittian, Kenneth R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2003-09</date><risdate>2003</risdate><volume>86</volume><issue>6</issue><spage>1545</spage><epage>1552</epage><pages>1545-1552</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Obstructive sleep apnea (OSA) is a frequent medical condition characterized by intermittent hypoxia (IH) during sleep, and is associated with neurodegenerative changes in several brain regions along with learning deficits. We hypothesized that aging rats exposed to IH during sleep would be particularly susceptible. Young (3–4 months) and aging (20–22 months) Sprague–Dawley rats were therefore exposed to either room air or IH for 14 days. Learning and memory was assessed with a standard place‐training version of the Morris water maze. Aging rats exposed to room air (RA) or IH displayed significant spatial learning impairments compared with similarly exposed young rats; furthermore, the decrements in performance between RA and IH were markedly greater in aging compared with young rats (p < 0.01), and coincided with the magnitude of IH‐induced decreases in cyclic AMP response element binding (CREB) phosphorylation. Furthermore, decreases in proteasomal activity occurred in both young and aging rats exposed to IH, but were substantially greater in the latter (p < 0.001). Neuronal apoptosis, as shown by cleaved caspase 3 expression, was particularly increased in aging rats exposed to IH (p < 0.01 versus young rats exposed to IH). Collectively, these findings indicate unique vulnerability of the aging rodent brain to IH, which is reflected at least in part, by the more prominent decreases in CREB phosphorylation and a marked inability of the ubiquitin‐proteasomal pathway to adequately clear degraded proteins.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12950463</pmid><doi>10.1046/j.1471-4159.2003.01973.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | aging Aging - metabolism Animals Apoptosis Biological and medical sciences Caspase 3 Caspases - metabolism Cyclic AMP Response Element-Binding Protein - metabolism Cysteine Endopeptidases - metabolism Hypoxia - physiopathology intermittent hypoxia Maze Learning Medical sciences Multienzyme Complexes - metabolism Nervous system involvement in other diseases. Miscellaneous Neurology Neurons - metabolism Neurons - pathology Phosphorylation proteasome Proteasome Endopeptidase Complex Rats Rats, Sprague-Dawley sleep apnea Sleep Apnea, Obstructive - physiopathology Spatial Behavior spatial learning |
| title | Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function |
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