5‐HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation‐induced NLRP3 activity
Postoperative delirium is a common complication that often results in poor outcomes in surgical and elderly patients. Accumulating evidences suggest that the pathophysiology of delirium results from multiple neurotransmitter system dysfunctions. To further clarify the effects of the selective seroto...
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| description | Postoperative delirium is a common complication that often results in poor outcomes in surgical and elderly patients. Accumulating evidences suggest that the pathophysiology of delirium results from multiple neurotransmitter system dysfunctions. To further clarify the effects of the selective serotonin (5‐HT) (1A) antagonist WAY‐100635 on the behaviors in scopolamine induced‐delirium rats and to explore the molecular mechanism, in this study, we investigated the change of monoamine levels in the cerebrospinal fluid (CSF) and different brain regions using high‐performance liquid chromatography and assessed the behavioral retrieval of delirium rats treated with WAY‐100635. It was found that 5‐hydroxy‐3‐indoleacetic acid (5‐HIAA), 3,4‐dihydroxyphenylacetic acid, and homovanillic acid concentrations in the CSF of scopolamine‐induced delirium rats were significantly increased, among which 5‐HIAA was also increased in hippocampus and basolateral amygdala (BLA), and 5‐HT(1A) receptor was significantly higher in the hippocampuses and BLA than other brain regions. Furthermore, intrahippocampus and intra‐BLA stereotactic injection of WAY‐100635 improved the delirium‐like behavior of rats. Mechanistically, after WAY‐100635 treatment, significant reduction of IL‐1β release into CSF and NOD‐like receptor family, pyrin domain containing 3 (NLRP3) expression, phosphorylated phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (AKT), and S6K was observed. Altogether, these results suggest that delirium rats induced by scopolamine may be correlated with an increased cerebral concentration of 5‐HT and dopamine neurotransmitters system; the selective 5‐HT(1A) antagoniszts can reverse the delirium symptoms at some extent through tendering PI3K/Akt/mammalian target of rapamycin complex 1 (mTOR) activation‐induced NLRP3 activity and then reducing IL‐1β release. © 2016 IUBMB Life, 68(4):311–319, 2016 |
| doi_str_mv | 10.1002/iub.1491 |
| format | Article |
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Accumulating evidences suggest that the pathophysiology of delirium results from multiple neurotransmitter system dysfunctions. To further clarify the effects of the selective serotonin (5‐HT) (1A) antagonist WAY‐100635 on the behaviors in scopolamine induced‐delirium rats and to explore the molecular mechanism, in this study, we investigated the change of monoamine levels in the cerebrospinal fluid (CSF) and different brain regions using high‐performance liquid chromatography and assessed the behavioral retrieval of delirium rats treated with WAY‐100635. It was found that 5‐hydroxy‐3‐indoleacetic acid (5‐HIAA), 3,4‐dihydroxyphenylacetic acid, and homovanillic acid concentrations in the CSF of scopolamine‐induced delirium rats were significantly increased, among which 5‐HIAA was also increased in hippocampus and basolateral amygdala (BLA), and 5‐HT(1A) receptor was significantly higher in the hippocampuses and BLA than other brain regions. Furthermore, intrahippocampus and intra‐BLA stereotactic injection of WAY‐100635 improved the delirium‐like behavior of rats. Mechanistically, after WAY‐100635 treatment, significant reduction of IL‐1β release into CSF and NOD‐like receptor family, pyrin domain containing 3 (NLRP3) expression, phosphorylated phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (AKT), and S6K was observed. Altogether, these results suggest that delirium rats induced by scopolamine may be correlated with an increased cerebral concentration of 5‐HT and dopamine neurotransmitters system; the selective 5‐HT(1A) antagoniszts can reverse the delirium symptoms at some extent through tendering PI3K/Akt/mammalian target of rapamycin complex 1 (mTOR) activation‐induced NLRP3 activity and then reducing IL‐1β release. © 2016 IUBMB Life, 68(4):311–319, 2016</description><identifier>ISSN: 1521-6543</identifier><identifier>EISSN: 1521-6551</identifier><identifier>DOI: 10.1002/iub.1491</identifier><identifier>PMID: 26946964</identifier><identifier>CODEN: IULIF8</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject><![CDATA[3,4-Dihydroxyphenylacetic Acid - cerebrospinal fluid ; 5‐HT(1A) receptor antagonist ; amygdala ; Animals ; Basolateral Nuclear Complex - drug effects ; Basolateral Nuclear Complex - metabolism ; Basolateral Nuclear Complex - physiopathology ; Emergence Delirium - cerebrospinal fluid ; Emergence Delirium - chemically induced ; Emergence Delirium - physiopathology ; Emergence Delirium - prevention & control ; Gene Expression Regulation ; hippocampus ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hippocampus - physiopathology ; Homovanillic Acid - cerebrospinal fluid ; Humans ; Hydroxyindoleacetic Acid - cerebrospinal fluid ; Injections, Intraventricular ; Interleukin-1beta - antagonists & inhibitors ; Interleukin-1beta - cerebrospinal fluid ; Interleukin-1beta - genetics ; Male ; Maze Learning - drug effects ; neuroinflammation ; neurotransmitter ; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein - cerebrospinal fluid ; NLR Family, Pyrin Domain-Containing 3 Protein - genetics ; Phosphatidylinositol 3-Kinase - antagonists & inhibitors ; Phosphatidylinositol 3-Kinase - cerebrospinal fluid ; Phosphatidylinositol 3-Kinase - genetics ; Piperazines - pharmacology ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - cerebrospinal fluid ; Proto-Oncogene Proteins c-akt - genetics ; Pyridines - pharmacology ; Rats ; Rats, Wistar ; Receptor, Serotonin, 5-HT1A - genetics ; Receptor, Serotonin, 5-HT1A - metabolism ; Scopolamine Hydrobromide ; Serotonin - cerebrospinal fluid ; Serotonin Antagonists - pharmacology ; Signal Transduction ; Stereotaxic Techniques ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; TOR Serine-Threonine Kinases - cerebrospinal fluid ; TOR Serine-Threonine Kinases - genetics]]></subject><ispartof>IUBMB life, 2016-04, Vol.68 (4), p.311-319</ispartof><rights>2016 International Union of Biochemistry and Molecular Biology</rights><rights>2016 International Union of Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4161-95f1478481b16206376dcfe0d7b4a14fb90b2e5806ab984a5f41673ba5954f003</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fiub.1491$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fiub.1491$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26946964$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiu, Yimin</creatorcontrib><creatorcontrib>Huang, Xiaojing</creatorcontrib><creatorcontrib>Huang, Lina</creatorcontrib><creatorcontrib>Tang, Liang</creatorcontrib><creatorcontrib>Jiang, Jihong</creatorcontrib><creatorcontrib>Chen, Lianhua</creatorcontrib><creatorcontrib>Li, Shitong</creatorcontrib><title>5‐HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation‐induced NLRP3 activity</title><title>IUBMB life</title><addtitle>IUBMB Life</addtitle><description>Postoperative delirium is a common complication that often results in poor outcomes in surgical and elderly patients. Accumulating evidences suggest that the pathophysiology of delirium results from multiple neurotransmitter system dysfunctions. To further clarify the effects of the selective serotonin (5‐HT) (1A) antagonist WAY‐100635 on the behaviors in scopolamine induced‐delirium rats and to explore the molecular mechanism, in this study, we investigated the change of monoamine levels in the cerebrospinal fluid (CSF) and different brain regions using high‐performance liquid chromatography and assessed the behavioral retrieval of delirium rats treated with WAY‐100635. It was found that 5‐hydroxy‐3‐indoleacetic acid (5‐HIAA), 3,4‐dihydroxyphenylacetic acid, and homovanillic acid concentrations in the CSF of scopolamine‐induced delirium rats were significantly increased, among which 5‐HIAA was also increased in hippocampus and basolateral amygdala (BLA), and 5‐HT(1A) receptor was significantly higher in the hippocampuses and BLA than other brain regions. Furthermore, intrahippocampus and intra‐BLA stereotactic injection of WAY‐100635 improved the delirium‐like behavior of rats. Mechanistically, after WAY‐100635 treatment, significant reduction of IL‐1β release into CSF and NOD‐like receptor family, pyrin domain containing 3 (NLRP3) expression, phosphorylated phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (AKT), and S6K was observed. Altogether, these results suggest that delirium rats induced by scopolamine may be correlated with an increased cerebral concentration of 5‐HT and dopamine neurotransmitters system; the selective 5‐HT(1A) antagoniszts can reverse the delirium symptoms at some extent through tendering PI3K/Akt/mammalian target of rapamycin complex 1 (mTOR) activation‐induced NLRP3 activity and then reducing IL‐1β release. © 2016 IUBMB Life, 68(4):311–319, 2016</description><subject>3,4-Dihydroxyphenylacetic Acid - cerebrospinal fluid</subject><subject>5‐HT(1A) receptor antagonist</subject><subject>amygdala</subject><subject>Animals</subject><subject>Basolateral Nuclear Complex - drug effects</subject><subject>Basolateral Nuclear Complex - metabolism</subject><subject>Basolateral Nuclear Complex - physiopathology</subject><subject>Emergence Delirium - cerebrospinal fluid</subject><subject>Emergence Delirium - chemically induced</subject><subject>Emergence Delirium - physiopathology</subject><subject>Emergence Delirium - prevention & control</subject><subject>Gene Expression Regulation</subject><subject>hippocampus</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - physiopathology</subject><subject>Homovanillic Acid - cerebrospinal fluid</subject><subject>Humans</subject><subject>Hydroxyindoleacetic Acid - cerebrospinal fluid</subject><subject>Injections, Intraventricular</subject><subject>Interleukin-1beta - antagonists & inhibitors</subject><subject>Interleukin-1beta - cerebrospinal fluid</subject><subject>Interleukin-1beta - genetics</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>neuroinflammation</subject><subject>neurotransmitter</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - cerebrospinal fluid</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - genetics</subject><subject>Phosphatidylinositol 3-Kinase - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinase - cerebrospinal fluid</subject><subject>Phosphatidylinositol 3-Kinase - genetics</subject><subject>Piperazines - pharmacology</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - cerebrospinal fluid</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Pyridines - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Serotonin, 5-HT1A - genetics</subject><subject>Receptor, Serotonin, 5-HT1A - metabolism</subject><subject>Scopolamine Hydrobromide</subject><subject>Serotonin - cerebrospinal fluid</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Signal Transduction</subject><subject>Stereotaxic Techniques</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>TOR Serine-Threonine Kinases - cerebrospinal fluid</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><issn>1521-6543</issn><issn>1521-6551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1uEzEUhS0EoqUg8QTIEpuymMYe_8x4GSqgERGtqnQ9smc8yS0zdmp7grLjERCPyJPgKKULvDmWznevfe9B6C0lF5SQcgaTuaBc0WfolIqSFlII-vzpztkJehXjPcmnIuolOiml4lJJfop-iz8_f12tzun8Aw62tdvkA9Yu6bV3EBOGcRv8zkZs7EbvIJtbG3ofRu1ai32POztAgGnEQaeI0yb4ab3B4DZgIIFb45sF-zqbf0-zcXV9i3WbYKcTeJffBddNre3wt-XtDTtakPav0YteD9G-edQzdPf50-ryqlhef1lczpdFy6mkhRI95VXNa2qoLIlkleza3pKuMlxT3htFTGlFTaQ2quZa9LmsYkYLJXhPCDtD58e-ecKHycbUjBBbOwzaWT_FhlaVkIwoVWb0_X_ovZ-Cy787ULxiNZM8U-8eqcmMtmu2AUYd9s2_bWegOAI_YLD7J5-S5pBik1NsDik2i7uPB2V_AWcckAA</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Qiu, Yimin</creator><creator>Huang, Xiaojing</creator><creator>Huang, Lina</creator><creator>Tang, Liang</creator><creator>Jiang, Jihong</creator><creator>Chen, Lianhua</creator><creator>Li, Shitong</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201604</creationdate><title>5‐HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation‐induced NLRP3 activity</title><author>Qiu, Yimin ; Huang, Xiaojing ; Huang, Lina ; Tang, Liang ; Jiang, Jihong ; Chen, Lianhua ; Li, Shitong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4161-95f1478481b16206376dcfe0d7b4a14fb90b2e5806ab984a5f41673ba5954f003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3,4-Dihydroxyphenylacetic Acid - cerebrospinal fluid</topic><topic>5‐HT(1A) receptor antagonist</topic><topic>amygdala</topic><topic>Animals</topic><topic>Basolateral Nuclear Complex - drug effects</topic><topic>Basolateral Nuclear Complex - metabolism</topic><topic>Basolateral Nuclear Complex - physiopathology</topic><topic>Emergence Delirium - cerebrospinal fluid</topic><topic>Emergence Delirium - chemically induced</topic><topic>Emergence Delirium - physiopathology</topic><topic>Emergence Delirium - prevention & control</topic><topic>Gene Expression Regulation</topic><topic>hippocampus</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - physiopathology</topic><topic>Homovanillic Acid - cerebrospinal fluid</topic><topic>Humans</topic><topic>Hydroxyindoleacetic Acid - cerebrospinal fluid</topic><topic>Injections, Intraventricular</topic><topic>Interleukin-1beta - antagonists & inhibitors</topic><topic>Interleukin-1beta - cerebrospinal fluid</topic><topic>Interleukin-1beta - genetics</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>neuroinflammation</topic><topic>neurotransmitter</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - cerebrospinal fluid</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - genetics</topic><topic>Phosphatidylinositol 3-Kinase - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinase - cerebrospinal fluid</topic><topic>Phosphatidylinositol 3-Kinase - genetics</topic><topic>Piperazines - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - cerebrospinal fluid</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Pyridines - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Serotonin, 5-HT1A - genetics</topic><topic>Receptor, Serotonin, 5-HT1A - metabolism</topic><topic>Scopolamine Hydrobromide</topic><topic>Serotonin - cerebrospinal fluid</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Signal Transduction</topic><topic>Stereotaxic Techniques</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>TOR Serine-Threonine Kinases - cerebrospinal fluid</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiu, Yimin</creatorcontrib><creatorcontrib>Huang, Xiaojing</creatorcontrib><creatorcontrib>Huang, Lina</creatorcontrib><creatorcontrib>Tang, Liang</creatorcontrib><creatorcontrib>Jiang, Jihong</creatorcontrib><creatorcontrib>Chen, Lianhua</creatorcontrib><creatorcontrib>Li, Shitong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>IUBMB life</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiu, Yimin</au><au>Huang, Xiaojing</au><au>Huang, Lina</au><au>Tang, Liang</au><au>Jiang, Jihong</au><au>Chen, Lianhua</au><au>Li, Shitong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5‐HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation‐induced NLRP3 activity</atitle><jtitle>IUBMB life</jtitle><addtitle>IUBMB Life</addtitle><date>2016-04</date><risdate>2016</risdate><volume>68</volume><issue>4</issue><spage>311</spage><epage>319</epage><pages>311-319</pages><issn>1521-6543</issn><eissn>1521-6551</eissn><coden>IULIF8</coden><abstract>Postoperative delirium is a common complication that often results in poor outcomes in surgical and elderly patients. Accumulating evidences suggest that the pathophysiology of delirium results from multiple neurotransmitter system dysfunctions. To further clarify the effects of the selective serotonin (5‐HT) (1A) antagonist WAY‐100635 on the behaviors in scopolamine induced‐delirium rats and to explore the molecular mechanism, in this study, we investigated the change of monoamine levels in the cerebrospinal fluid (CSF) and different brain regions using high‐performance liquid chromatography and assessed the behavioral retrieval of delirium rats treated with WAY‐100635. It was found that 5‐hydroxy‐3‐indoleacetic acid (5‐HIAA), 3,4‐dihydroxyphenylacetic acid, and homovanillic acid concentrations in the CSF of scopolamine‐induced delirium rats were significantly increased, among which 5‐HIAA was also increased in hippocampus and basolateral amygdala (BLA), and 5‐HT(1A) receptor was significantly higher in the hippocampuses and BLA than other brain regions. Furthermore, intrahippocampus and intra‐BLA stereotactic injection of WAY‐100635 improved the delirium‐like behavior of rats. Mechanistically, after WAY‐100635 treatment, significant reduction of IL‐1β release into CSF and NOD‐like receptor family, pyrin domain containing 3 (NLRP3) expression, phosphorylated phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (AKT), and S6K was observed. Altogether, these results suggest that delirium rats induced by scopolamine may be correlated with an increased cerebral concentration of 5‐HT and dopamine neurotransmitters system; the selective 5‐HT(1A) antagoniszts can reverse the delirium symptoms at some extent through tendering PI3K/Akt/mammalian target of rapamycin complex 1 (mTOR) activation‐induced NLRP3 activity and then reducing IL‐1β release. © 2016 IUBMB Life, 68(4):311–319, 2016</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26946964</pmid><doi>10.1002/iub.1491</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3,4-Dihydroxyphenylacetic Acid - cerebrospinal fluid 5‐HT(1A) receptor antagonist amygdala Animals Basolateral Nuclear Complex - drug effects Basolateral Nuclear Complex - metabolism Basolateral Nuclear Complex - physiopathology Emergence Delirium - cerebrospinal fluid Emergence Delirium - chemically induced Emergence Delirium - physiopathology Emergence Delirium - prevention & control Gene Expression Regulation hippocampus Hippocampus - drug effects Hippocampus - metabolism Hippocampus - physiopathology Homovanillic Acid - cerebrospinal fluid Humans Hydroxyindoleacetic Acid - cerebrospinal fluid Injections, Intraventricular Interleukin-1beta - antagonists & inhibitors Interleukin-1beta - cerebrospinal fluid Interleukin-1beta - genetics Male Maze Learning - drug effects neuroinflammation neurotransmitter NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors NLR Family, Pyrin Domain-Containing 3 Protein - cerebrospinal fluid NLR Family, Pyrin Domain-Containing 3 Protein - genetics Phosphatidylinositol 3-Kinase - antagonists & inhibitors Phosphatidylinositol 3-Kinase - cerebrospinal fluid Phosphatidylinositol 3-Kinase - genetics Piperazines - pharmacology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - cerebrospinal fluid Proto-Oncogene Proteins c-akt - genetics Pyridines - pharmacology Rats Rats, Wistar Receptor, Serotonin, 5-HT1A - genetics Receptor, Serotonin, 5-HT1A - metabolism Scopolamine Hydrobromide Serotonin - cerebrospinal fluid Serotonin Antagonists - pharmacology Signal Transduction Stereotaxic Techniques TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - cerebrospinal fluid TOR Serine-Threonine Kinases - genetics |
| title | 5‐HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation‐induced NLRP3 activity |
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