Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism
Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment s...
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| Veröffentlicht in: | Journal of pineal research 2014-01, Vol.56 (1), p.1-11 |
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| creator | Tian, Yun Yabuki, Yasushi Moriguchi, Shigeki Fukunaga, Kohji Mao, Pei-Jiang Hong, Ling-Juan Lu, Ying-Mei Wang, Rui Ahmed, Muhammad Masood Liao, Mei-Hua Huang, Ji-Yun Zhang, Rui-Ting Zhou, Tian-Yi Long, Sen Han, Feng |
| description | Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)‐induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho‐CaMKII (Thr286) in the hippocampus of VPA‐treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin‐treated rat, long‐term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 ± 3.9% of the baseline, P |
| doi_str_mv | 10.1111/jpi.12081 |
| format | Article |
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This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)‐induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho‐CaMKII (Thr286) in the hippocampus of VPA‐treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin‐treated rat, long‐term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 ± 3.9% of the baseline, P < 0.01 versus VPA‐treated rats) following high‐frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in VPA‐treated rats. Taken together, the increased phosphorylation of CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin on autism symptoms.</description><identifier>ISSN: 0742-3098</identifier><identifier>EISSN: 1600-079X</identifier><identifier>DOI: 10.1111/jpi.12081</identifier><identifier>PMID: 23952810</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Analysis of Variance ; Animal models ; Animals ; Antioxidants - pharmacology ; autism ; Autistic Disorder ; Behavior, Animal - drug effects ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - analysis ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism ; CaMKII ; Disease Models, Animal ; Female ; hippocampus ; Hippocampus - chemistry ; Hippocampus - drug effects ; Hippocampus - enzymology ; Immunohistochemistry ; Male ; melatonin ; Melatonin - pharmacology ; phosphorylation ; Phosphorylation - drug effects ; Rats ; Rats, Sprague-Dawley ; valproic acid ; Valproic Acid - pharmacology</subject><ispartof>Journal of pineal research, 2014-01, Vol.56 (1), p.1-11</ispartof><rights>2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4621-2fd7b11e1d65e138971aa480a775c0d0edbc100e102f07253f5dd1e7c9be15e13</citedby><cites>FETCH-LOGICAL-c4621-2fd7b11e1d65e138971aa480a775c0d0edbc100e102f07253f5dd1e7c9be15e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjpi.12081$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjpi.12081$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23952810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Yun</creatorcontrib><creatorcontrib>Yabuki, Yasushi</creatorcontrib><creatorcontrib>Moriguchi, Shigeki</creatorcontrib><creatorcontrib>Fukunaga, Kohji</creatorcontrib><creatorcontrib>Mao, Pei-Jiang</creatorcontrib><creatorcontrib>Hong, Ling-Juan</creatorcontrib><creatorcontrib>Lu, Ying-Mei</creatorcontrib><creatorcontrib>Wang, Rui</creatorcontrib><creatorcontrib>Ahmed, Muhammad Masood</creatorcontrib><creatorcontrib>Liao, Mei-Hua</creatorcontrib><creatorcontrib>Huang, Ji-Yun</creatorcontrib><creatorcontrib>Zhang, Rui-Ting</creatorcontrib><creatorcontrib>Zhou, Tian-Yi</creatorcontrib><creatorcontrib>Long, Sen</creatorcontrib><creatorcontrib>Han, Feng</creatorcontrib><title>Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism</title><title>Journal of pineal research</title><addtitle>J. Pineal Res</addtitle><description>Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)‐induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho‐CaMKII (Thr286) in the hippocampus of VPA‐treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin‐treated rat, long‐term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 ± 3.9% of the baseline, P < 0.01 versus VPA‐treated rats) following high‐frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in VPA‐treated rats. Taken together, the increased phosphorylation of CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin on autism symptoms.</description><subject>Analysis of Variance</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>autism</subject><subject>Autistic Disorder</subject><subject>Behavior, Animal - drug effects</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - analysis</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</subject><subject>CaMKII</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>hippocampus</subject><subject>Hippocampus - chemistry</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - enzymology</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>melatonin</subject><subject>Melatonin - pharmacology</subject><subject>phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>valproic acid</subject><subject>Valproic Acid - pharmacology</subject><issn>0742-3098</issn><issn>1600-079X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1OGzEUha2qqAm0i75ANcuyGHKv58eeZYUgUFHaRSuyszzjO4rD_NWeBHh7PCSww7Jk2f6-o6vD2FeEMwxrsRnsGXKQ-IHNMQeIQRSrj2wOIuVxAoWcsWPvNwAgpcw_sRlPioxLhDnb_aJGj31nu8jRjpwnH41rigxVjvR0Cz9rOwx9pdtBN9Hg-pHCmydnO1qMa0eTTdG97V74vgxfOzKTqKdt26C1vaEm6utIb0fr28_sqNaNpy-H84T9u7z4e34V3_xeXp__uImrNOcY89qIEpHQ5BlhIguBWqcStBBZBQbIlBUCEAKvQfAsqTNjkERVlISTccK-73PD2P-35EfVWl9R0-iO-q1XmBY8T7EQMqCne7RyvfeOajW4MLp7UghqqlmFmtVLzYH9dojdli2ZN_K11wAs9sCDbejp_ST188_1a2S8N6wf6fHN0O5e5SIRmbq7XapVgpng-Z26TZ4BQyyXtQ</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Tian, Yun</creator><creator>Yabuki, Yasushi</creator><creator>Moriguchi, Shigeki</creator><creator>Fukunaga, Kohji</creator><creator>Mao, Pei-Jiang</creator><creator>Hong, Ling-Juan</creator><creator>Lu, Ying-Mei</creator><creator>Wang, Rui</creator><creator>Ahmed, Muhammad Masood</creator><creator>Liao, Mei-Hua</creator><creator>Huang, Ji-Yun</creator><creator>Zhang, Rui-Ting</creator><creator>Zhou, Tian-Yi</creator><creator>Long, Sen</creator><creator>Han, Feng</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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></search><sort><creationdate>201401</creationdate><title>Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism</title><author>Tian, Yun ; Yabuki, Yasushi ; Moriguchi, Shigeki ; Fukunaga, Kohji ; Mao, Pei-Jiang ; Hong, Ling-Juan ; Lu, Ying-Mei ; Wang, Rui ; Ahmed, Muhammad Masood ; Liao, Mei-Hua ; Huang, Ji-Yun ; Zhang, Rui-Ting ; Zhou, Tian-Yi ; Long, Sen ; Han, Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4621-2fd7b11e1d65e138971aa480a775c0d0edbc100e102f07253f5dd1e7c9be15e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis of Variance</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>autism</topic><topic>Autistic Disorder</topic><topic>Behavior, Animal - drug effects</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - analysis</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</topic><topic>CaMKII</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>hippocampus</topic><topic>Hippocampus - chemistry</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - enzymology</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>melatonin</topic><topic>Melatonin - pharmacology</topic><topic>phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>valproic acid</topic><topic>Valproic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Yun</creatorcontrib><creatorcontrib>Yabuki, Yasushi</creatorcontrib><creatorcontrib>Moriguchi, Shigeki</creatorcontrib><creatorcontrib>Fukunaga, Kohji</creatorcontrib><creatorcontrib>Mao, Pei-Jiang</creatorcontrib><creatorcontrib>Hong, Ling-Juan</creatorcontrib><creatorcontrib>Lu, Ying-Mei</creatorcontrib><creatorcontrib>Wang, Rui</creatorcontrib><creatorcontrib>Ahmed, Muhammad Masood</creatorcontrib><creatorcontrib>Liao, Mei-Hua</creatorcontrib><creatorcontrib>Huang, Ji-Yun</creatorcontrib><creatorcontrib>Zhang, Rui-Ting</creatorcontrib><creatorcontrib>Zhou, Tian-Yi</creatorcontrib><creatorcontrib>Long, Sen</creatorcontrib><creatorcontrib>Han, Feng</creatorcontrib><collection>Istex</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><jtitle>Journal of pineal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tian, Yun</au><au>Yabuki, Yasushi</au><au>Moriguchi, Shigeki</au><au>Fukunaga, Kohji</au><au>Mao, Pei-Jiang</au><au>Hong, Ling-Juan</au><au>Lu, Ying-Mei</au><au>Wang, Rui</au><au>Ahmed, Muhammad Masood</au><au>Liao, Mei-Hua</au><au>Huang, Ji-Yun</au><au>Zhang, Rui-Ting</au><au>Zhou, Tian-Yi</au><au>Long, Sen</au><au>Han, Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism</atitle><jtitle>Journal of pineal research</jtitle><addtitle>J. Pineal Res</addtitle><date>2014-01</date><risdate>2014</risdate><volume>56</volume><issue>1</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0742-3098</issn><eissn>1600-079X</eissn><abstract>Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)‐induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho‐CaMKII (Thr286) in the hippocampus of VPA‐treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin‐treated rat, long‐term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 ± 3.9% of the baseline, P < 0.01 versus VPA‐treated rats) following high‐frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in VPA‐treated rats. Taken together, the increased phosphorylation of CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin on autism symptoms.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23952810</pmid><doi>10.1111/jpi.12081</doi><tpages>11</tpages></addata></record> |
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| subjects | Analysis of Variance Animal models Animals Antioxidants - pharmacology autism Autistic Disorder Behavior, Animal - drug effects Calcium-Calmodulin-Dependent Protein Kinase Type 2 - analysis Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism CaMKII Disease Models, Animal Female hippocampus Hippocampus - chemistry Hippocampus - drug effects Hippocampus - enzymology Immunohistochemistry Male melatonin Melatonin - pharmacology phosphorylation Phosphorylation - drug effects Rats Rats, Sprague-Dawley valproic acid Valproic Acid - pharmacology |
| title | Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism |
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