auditory-brainstem-response-outer-hair-cell-whole-cell-patch-clamp

Auditory Brainstem Response and Outer Hair Cell Whole-cell Patch Clamp Recording in Postnatal Rats

The outer hair cell is one of the two types of sensory hair cells in the mammalian cochlea. They alter their cell length with the receptor potential to ...

Southern Medical University

Recent studies have shown that leptin (an adipocytokine) played an important role in nociceptive behavior induced by nerve injury, but the cellular mechanism of this action remains unclear. Using the whole-cell patch-clamp recording from rat's spinal cord slices, we showed that superfusion of leptin onto spinal cord slices dose-dependently enhanced N-methyl-d-aspartate (NMDA) receptor-mediated currents in spinal cord lamina II neurons. At the cellular level, the effect of leptin on spinal NMDA-induced currents was mediated through the leptin receptor and the JAK2/STAT3 (but not PI3K or MAPK) pathway, as the leptin effect was abolished in leptin receptor-deficient (db/db) mice and inhibited by a JAK/STAT inhibitor. Moreover, we demonstrated in naïve rats that a single intrathecal administration of leptin enhanced spontaneous biting, scratching, and licking behavior induced by intrathecal NMDA and that repeated intrathecal administration of leptin elicited thermal hyperalgesia and mechanical allodynia, which was attenuated by the noncompetitive NMDA receptor antagonist MK-801. Intrathecal leptin also upregulated the expression of NMDA receptors and pSTAT3 within the rat's spinal cord dorsal horn, and intrathecal MK-801 attenuated this leptin effect as well. Our data demonstrate a relationship between leptin and NMDA receptor-mediated spinal neuronal excitation and its functional role in nociceptive behavior. Since leptin contributes to nociceptive behavior induced by nerve injury, the present findings suggest an important cellular link between the leptin's spinal effect and the NMDA receptor-mediated cellular mechanism of neuropathic pain. A functional link is demonstrated between leptin, an adipocytokine, and the cellular mechanisms of neuropathic pain via enhancement of function and expression of spinal N-methyl-d-aspartate receptors.

Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain.

&#x75BC;&#x75DB;&#x548C;&#x6291;&#x90C1;&#x4E4B;&#x95F4;&#x7684;&#x8FDE;&#x63A5;&#x65E9;&#x5DF2;&#x5F97;&#x5230;&#x627F;&#x8BA4;&#x5728;&#x4E34;&#x5E8A;&#x7684;&#x8BBE;&#x7F6E; &#xFF1B;&#x7136;&#x800C;&#xFF0C;&#x5176;&#x673A;&#x5236;&#x4ECD;&#x4E0D;&#x6E05;&#x695A;&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x8868;&#x660E;&#x5355;&#x65B9;&#x9762;&#x989E;&#x4E0B;&#x988C;&#x5173;&#x8282; (&#x989E;&#x4E0B;&#x988C;&#x5173;&#x8282;) &#x53D1;&#x708E;&#x6240;&#x81F4;&#xFF0C;&#x673A;&#x68B0;&#x75DB;&#x89C9;&#x8FC7;&#x654F;&#x5927;&#x9F20;&#x4EAC;&#x90FD; (WKY) &#x5927;&#x9F20;&#x57FA;&#x56E0;&#x6613;&#x611F;&#x6291;&#x90C1;&#x884C;&#x4E3A;&#x800C;&#x6076;&#x5316;&#x3002;&#x53CD;&#x8FC7;&#x6765;&#x8BF4;&#xFF0C;&#x989E;&#x4E0B;&#x988C;&#x5173;&#x8282;&#x53D1;&#x708E;&#x589E;&#x5F3A;&#x6291;&#x90C1;&#x7684;&#x884C;&#x4E3A;&#xFF0C;&#x8FD9;&#x6837;&#x4F4E;&#x7684;&#x75DB;&#x89C9;&#x9608;&#x503C;&#x4E0E;&#x5206;&#x6570;&#x8D8A;&#x9AD8;&#x7684;&#x540C;&#x4E00; WKY &#x5927;&#x9F20;&#x6291;&#x90C1;&#x884C;&#x4E3A;&#x76F8;&#x5173;&#x3002;&#x5927;&#x9F20;&#xFF0C;&#x800C; WKY &#x5927;&#x9F20;&#x540C;&#x4FA7;&#x4E09;&#x53C9;&#x795E;&#x7ECF;&#x4FA7;&#x4E9A;&#x6838; caudalis (Sp5C) &#x8868;&#x660E;&#x4F4E;&#x8840;&#x6D46;&#x892A;&#x9ED1;&#x6FC0;&#x7D20;&#x6C34;&#x5E73;&#xFF0C;&#x4E0B;&#x8C03;&#x7684;&#x892A;&#x9ED1;&#x7D20; MT1 &#x53D7;&#x4F53;&#xFF0C;&#x4F46; NR1 &#x4E9A;&#x5355;&#x4F4D;&#x7684; NMDA &#x53D7;&#x4F53;&#x7684;&#x8868;&#x8FBE;&#x4E0A;&#x8C03;&#x3002;6 Chloromelatonin &#x8111;&#x6C60;&#x7BA1;&#x7406; &#xFF08;250&mu;g&#xFF0C;7 &#x5929;&#xFF0C;&#x6BCF;&#x5929;&#x4E24;&#x6B21;&#xFF09; &#x540C;&#x65F6;&#x51CF;&#x6BD2;&#x673A;&#x68B0;&#x75DB;&#x89C9;&#x8FC7;&#x654F;&#x548C; WKY &#x5927;&#x9F20;&#x6291;&#x90C1;&#x884C;&#x4E3A;&#x4EE5;&#x53CA;&#x540C;&#x4FA7;&#x7684; Sp5C &#x7F16;&#x7801; NR1 &#x8868;&#x8FBE;&#x3002;&#x5728;&#x819C;&#x7247;&#x94B3;&#x5F55;&#x97F3;&#xFF0C;&#x892A;&#x9ED1;&#x6FC0;&#x7D20;&#x5242;&#x91CF;&#x4F9D;&#x8D56;&#x6027;&#x4E0B;&#x964D;&#x5728;&#x810A;&#x9AD3;&#x80CC;&#x89D2;&#x80F6;&#x72B6;&#x8D28;&#x795E;&#x7ECF;&#x5143; NMDA &#x8BF1;&#x5BFC;&#x7535;&#x6D41;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x989E;&#x4E0B;&#x988C;&#x5173;&#x8282;&#x53D1;&#x708E;&#x5F15;&#x8D77;&#x7684;&#x673A;&#x68B0;&#x75DB;&#x89C9;&#x8FC7;&#x654F;&#x548C;&#x6291;&#x90C1;&#x884C;&#x4E3A;&#x4E4B;&#x95F4;&#x7684;&#x4E92;&#x60E0;&#x5173;&#x7CFB;&#xFF0C;&#x5E76;&#x5EFA;&#x8BAE;&#x4E2D;&#x592E; melatoninergic &#x7CFB;&#x7EDF;&#xFF0C;&#x901A;&#x8FC7;&#x8C03;&#x5236;&#x7684; NMDA &#x53D7;&#x4F53;&#x7684;&#x8868;&#x8FBE;&#x53CA;&#x6D3B;&#x6027;&#xFF0C;&#x53EF;&#x80FD;&#x4F5C;&#x7528;&#x673A;&#x5236;&#x4E4B;&#x95F4;&#x75BC;&#x75DB;&#x548C;&#x6291;&#x90C1;&#x5171;&#x75C5;&#x3002;

&#x5927;&#x9F20;&#x57FA;&#x56E0;&#x6613;&#x611F;&#x6291;&#x90C1;&#x884C;&#x4E3A;&#x52A0;&#x5267;&#x673A;&#x68B0;&#x75DB;&#x89C9;&#x8FC7;&#x654F;: &#x892A;&#x9ED1;&#x6FC0;&#x7D20;&#x548C; NMDA &#x53D7;&#x4F53;&#x7684;&#x4F5C;&#x7528;&#x3002;

A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. As compared with Wistar rats, WKY rats showed a lower plasma melatonin level, downregulation of the melatonin MT1 receptor, but upregulation of the NR1 subunit of the NMDA receptor in the ipsilateral trigeminal subnucleus caudalis (Sp5C). Intracisternal administration of 6-chloromelatonin (250Î¼g, twice daily for 7days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.

Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: Role of melatonin and NMDA receptors.

Un lien entre la douleur et la d&eacute;pression est reconnu depuis longtemps dans le milieu clinique ; Cependant, son m&eacute;canisme reste peu clair. Cette &eacute;tude a montr&eacute; que hyperalg&eacute;sie m&eacute;canique induite par l&#39;inflammation (ATM) unilat&eacute;rale des articulations temporo-mandibulaire a &eacute;t&eacute; exacerb&eacute;e chez les rats Wistar-Kyoto (WKY) avec un comportement d&eacute;pressif g&eacute;n&eacute;tiquement pr&eacute;dispos&eacute;. R&eacute;ciproquement, l&#39;inflammation TMJ am&eacute;lior&eacute; comportement d&eacute;pressif telle qu&#39;un seuil nociceptif en corr&eacute;lation avec un score plus &eacute;lev&eacute; de comportement d&eacute;pressif chez les rats WKY m&ecirc;mes. Comparativement aux rats Wistar, rats WKY a montr&eacute; un niveau de m&eacute;latonine plasmatique inf&eacute;rieur, diminution de l&#39;expression du r&eacute;cepteur de la m&eacute;latonine MT1, mais l&#39;augmentation de la sous-unit&eacute; NR1 du r&eacute;cepteur NMDA dans le subnucleus du trijumeau ipsilat&eacute;ral caudalis (Sp5C). Administration intracisternale de 6-chloromelatonin (250&mu;g, deux fois par jour pendant 7 jours) simultan&eacute;ment att&eacute;nu&eacute; hyperalg&eacute;sie m&eacute;canique et comportement d&eacute;pressif chez les rats WKY ainsi qu&#39;expression diminu&eacute;e le NR1 dans le Sp5C ipsilat&eacute;ral. Dans les enregistrements de patch-clamp, m&eacute;latonine dose accusait une diminution proportionnelle des courants induits par NMDA dans les neurones de la moelle &eacute;pini&egrave;re corne dorsale gelatinosa substantia. Ces r&eacute;sultats d&eacute;montrent une relation r&eacute;ciproque entre l&#39;hyperalg&eacute;sie m&eacute;canique induite par l&#39;inflammation de TMJ et comportement d&eacute;pressif et sugg&egrave;rent que le syst&egrave;me melatoninergic central, par le biais de la modulation de l&#39;activit&eacute; et l&#39;expression des r&eacute;cepteurs NMDA peut-&ecirc;tre jouer un r&ocirc;le dans les m&eacute;canismes de la comorbidit&eacute; entre la douleur et la d&eacute;pression.

Une hyperalg&eacute;sie m&eacute;canique exacerb&eacute;e chez les rats avec un comportement d&eacute;pressif g&eacute;n&eacute;tiquement pr&eacute;dispos&eacute; : r&ocirc;le de la m&eacute;latonine et des r&eacute;cepteurs NMDA.

Eine Verbindung zwischen Schmerz und Depression ist seit langem in der klinischen Einstellung anerkannt; Ihr Mechanismus bleibt jedoch unklar. Diese Studie zeigte, dass die mechanischen Hyperalgesie induziert durch einseitige Kiefergelenk (TMJ) Gelenkentz&uuml;ndungen an Wistar-Kyoto (WKY) Ratten mit genetisch veranlagt sein depressive Verhalten zuzuschreiben ist. Gegenseitig, verbessert TMJ Entz&uuml;ndung depressive Verhalten eine nozizeptive Selbstbeteiligung korreliert mit einer h&ouml;heren Punktzahl von depressiven Verhalten in der gleichen WKY-Ratten. Im Vergleich zu Wistar-Ratten zeigte WKY Ratten Plasma Melatonin niedriger, Heraufregulation des Melatonin MT1-Rezeptors, sondern Hochregulation von der NR1-Untereinheit des NMDA-Rezeptors in der ipsilateralen trigeminal Subnucleus Puffotter (Sp5C). Intracisternal Verwaltung des 6-Chloromelatonin (250&mu;g, zweimal t&auml;glich f&uuml;r 7 Tage) gleichzeitig abgeschw&auml;cht mechanischen Hyperalgesie und depressiven Verhalten bei WKY Ratten sowie Downregulated die NR1 Ausdruck in der ipsilateralen Sp5C. Bei Patch-Clamp-Aufnahmen verringerte Melatonin Dosis-abh&auml;ngige NMDA-induzierte Str&ouml;me im R&uuml;ckenmark Hinterhorn Substantia Gelatinosa Neuronen. Diese Ergebnisse zeigen eine reziproke Beziehung zwischen TMJ Entz&uuml;ndung induziert mechanischen Hyperalgesie und depressiven Verhalten und schlagen vor, da&szlig; das zentrale Melatoninergic-System, durch Modulation der NMDA-Rezeptor-Expression und Aktivit&auml;t, in die Mechanismen der Komorbidit&auml;t zwischen Schmerz und Depressionen eine Rolle spielen kann.

Exazerbierte mechanischen Hyperalgesie bei Ratten mit genetisch veranlagt sein depressive Verhalten: Rolle von Melatonin und NMDA-Rezeptoren.

Una connessione tra il dolore e la depressione ha da tempo riconosciuta in ambito clinico; Tuttavia, il suo meccanismo rimane poco chiaro. Questo studio ha mostrato che meccanica iperalgesia indotta dall&#39;infiammazione delle (ATM) articolazioni temporo-mandibolare unilaterale &egrave; stato aggravato in ratti Wistar-Kyoto (WKY) con comportamento depressivo geneticamente predisposto. Reciprocamente, infiammazione TMJ migliorato comportamento depressivo tale che una soglia inferiore nocicettivo correlato con un punteggio pi&ugrave; alto di comportamento depressivo in ratti WKY stessi. Rispetto ai ratti Wistar, ratti WKY ha mostrato un basso livello di melatonina plasma, downregulation del recettore MT1 melatonina, ma upregulation della subunit&agrave; NR1 del recettore NMDA nella subnucleus del trigemino omolaterale caudalis (Sp5C). Intracisternal amministrazione del 6-chloromelatonin (250&mu;g, due volte al giorno per 7 giorni) contemporaneamente attenuato iperalgesia meccanica e comportamento depressivo nei ratti WKY nonch&eacute; espressione downregolata il NR1 nella Sp5C omolaterale. Nelle registrazioni di patch-clamp, dose-dipendente di melatonina diminuita NMDA-indotta delle correnti nei neuroni del midollo spinale dorsale corno gelatinosa di substantia. Questi risultati dimostrano un rapporto di reciprocit&agrave; tra TMJ infiammazione indotta iperalgesia meccanica e comportamento depressivo e suggeriscono che il sistema melatoninergic centrale, attraverso la modulazione dell&#39;espressione dei recettori NMDA e attivit&agrave;, pu&ograve; svolgere un ruolo nei meccanismi della comorbidit&agrave; tra depressione e dolore.

Esacerbato iperalgesia meccanica nei ratti con comportamento depressivo geneticamente predisposto: ruolo della melatonina e i recettori NMDA.

&#x75DB;&#x307F;&#x3068;&#x3046;&#x3064;&#x75C5;&#x306E;&#x9593;&#x306E;&#x63A5;&#x7D9A;&#x306F;&#x3001;&#x9577;&#x3044;&#x81E8;&#x5E8A;&#x8A2D;&#x5B9A;&#x3067;&#x8A8D;&#x8B58;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;;&#x3057;&#x304B;&#x3057;&#x3001;&#x305D;&#x306E;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306F;&#x4E0D;&#x660E;&#x3067;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x7814;&#x7A76;&#x306F;&#x907A;&#x4F1D;&#x7684;&#x7D20;&#x56E0;&#x306E;&#x6291;&#x3046;&#x3064;&#x52D5;&#x4F5C; Wistar &#x4EAC;&#x90FD; (WKY) &#x30E9;&#x30C3;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x7247;&#x5074;&#x984E;&#x95A2;&#x7BC0; &#xFF08;TMJ&#xFF09; &#x306E;&#x708E;&#x75C7;&#x306B;&#x3088;&#x3063;&#x3066;&#x8A98;&#x8D77;&#x3055;&#x308C;&#x308B;&#x305D;&#x306E;&#x6A5F;&#x68B0;&#x7684;&#x75DB;&#x899A;&#x904E;&#x654F;&#x304C;&#x60AA;&#x5316;&#x3057;&#x305F;&#x793A;&#x3057;&#x305F;&#x3002;&#x75DB;&#x899A;&#x3057;&#x304D;&#x3044;&#x5024;&#x306E;&#x4E0B;&#x9650;&#x540C;&#x3058; WKY &#x30E9;&#x30C3;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x6291;&#x3046;&#x3064;&#x306E;&#x884C;&#x52D5;&#x306E;&#x30B9;&#x30B3;&#x30A2;&#x304C;&#x9AD8;&#x3044;&#x3068;&#x76F8;&#x95A2;&#x3059;&#x308B;&#x3088;&#x3046;&#x306B;&#x76F8;&#x4E92;&#x3001;&#x984E;&#x95A2;&#x7BC0;&#x708E;&#x75C7;&#x6291;&#x3046;&#x3064;&#x306E;&#x52D5;&#x4F5C;&#x3092;&#x62E1;&#x5F35;&#x3057;&#x307E;&#x3059;&#x3002;Wistar &#x30E9;&#x30C3;&#x30C8;&#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066; WKY &#x30E9;&#x30C3;&#x30C8;&#x3001;&#x4F4E;&#x3044;&#x30D7;&#x30E9;&#x30BA;&#x30DE; &#x30E1;&#x30E9;&#x30C8;&#x30CB;&#x30F3;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x3001;&#x30E1;&#x30E9;&#x30C8;&#x30CB;&#x30F3; MT1 &#x53D7;&#x5BB9;&#x306E;&#x30C0;&#x30A6;&#x30F3;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3057;&#x304B;&#x3057;&#x30A2;&#x30C3;&#x30D7;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306E; NR1 NMDA &#x53D7;&#x5BB9;&#x4F53;&#x30B5;&#x30D6;&#x30E6;&#x30CB;&#x30C3;&#x30C8;&#x306E;&#x540C;&#x5074;&#x306E;&#x4E09;&#x53C9;&#x795E;&#x7D4C;&#x810A;&#x9AC4;&#x8DEF; (Sp5C) &#x3067;&#x793A;&#x3057;&#x305F;&#x3002;6 Chloromelatonin &#x306E;&#x5927;&#x69FD;&#x5185;&#x30B9;&#x30C6;&#x30ED;&#x30A4;&#x30C9;&#x6295;&#x4E0E; (250 &mu; g&#x3001;7 &#x65E5;&#x9593; 1 &#x65E5; 2 &#x56DE;) &#x540C;&#x6642;&#x306B;&#x5F31;&#x6BD2;&#x6A5F;&#x68B0;&#x75DB;&#x899A;&#x904E;&#x654F;&#x3068; WKY &#x30E9;&#x30C3;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x6291;&#x3046;&#x3064;&#x306E;&#x884C;&#x52D5;&#x3060;&#x3051;&#x3067;&#x306A;&#x304F;&#x3001;&#x540C;&#x5074;&#x306E; Sp5C &#x3067; downregulated&#x3001;NR1 &#x5F0F;&#x3002;&#x30D1;&#x30C3;&#x30C1; &#x30FB; &#x30AF;&#x30E9;&#x30F3;&#x30D7;&#x306E;&#x9332;&#x97F3;&#x3067;&#x306F;&#x3001;&#x30E1;&#x30E9;&#x30C8;&#x30CB;&#x30F3;&#x306E;&#x7528;&#x91CF;-&#x72EC;&#x7ACB;&#x810A;&#x9AC4;&#x5F8C;&#x89D2;&#x306E;&#x81A0;&#x69D8;&#x8CEA;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E; NMDA &#x8A98;&#x8D77;&#x96FB;&#x6D41;&#x3092;&#x6E1B;&#x5C11;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x7D50;&#x679C;&#x306F;&#x984E;&#x95A2;&#x7BC0;&#x708E;&#x75C7;&#x8A98;&#x8D77;&#x6A5F;&#x68B0;&#x75DB;&#x899A;&#x904E;&#x654F;&#x3068;&#x6291;&#x3046;&#x3064;&#x6319;&#x52D5;&#x306E;&#x76F8;&#x4E92;&#x95A2;&#x4FC2;&#x3092;&#x793A;&#x3059;&#x305F;&#x3081;&#x3001;&#x4E2D;&#x592E; melatoninergic &#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x306E; NMDA &#x53D7;&#x5BB9;&#x4F53;&#x306E;&#x767A;&#x73FE;&#x3068;&#x6D3B;&#x52D5;&#x306E;&#x5909;&#x8ABF;&#x3092;&#x901A;&#x3057;&#x3066;&#x75DB;&#x307F;&#x3068;&#x3046;&#x3064;&#x75C5;&#x3068;&#x4F75;&#x5B58;&#x75BE;&#x60A3;&#x306E;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3067;&#x306F;&#x3001;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3059;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x60AA;&#x5316;&#x306E;&#x6A5F;&#x68B0;&#x75DB;&#x899A;&#x904E;&#x654F;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x907A;&#x4F1D;&#x7684;&#x7D20;&#x56E0;&#x306E;&#x6291;&#x3046;&#x3064;&#x306E;&#x884C;&#x52D5;: &#x30E1;&#x30E9;&#x30C8;&#x30CB;&#x30F3;&#x3068; NMDA &#x53D7;&#x5BB9;&#x4F53;&#x306E;&#x5F79;&#x5272;&#x3002;

&#xD1B5;&#xC99D;&#xACFC; &#xC6B0;&#xC6B8;&#xC99D; &#xC0AC;&#xC774;&#xC758; &#xC5F0;&#xACB0;&#xC744; &#xC624;&#xB798; &#xC784;&#xC0C1; &#xC124;&#xC815;;&#xC5D0;&#xC11C; &#xC778;&#xC815;&#xC744; &#xBC1B;&#xACE0; &#xC788;&#xB2E4; &#xADF8;&#xB7EC;&#xB098;, &#xADF8; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC774; &#xBD88;&#xBD84;&#xBA85; &#xB0A8;&#xC544; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xB294; &#xAE30;&#xACC4;&#xC801; hyperalgesia &#xC77C;&#xBC29;&#xC801;&#xC778; &#xD131; &#xAD00;&#xC808; (TMJ) &#xC5FC;&#xC99D;&#xC5D0; &#xC758;&#xD574; &#xC720;&#xB3C4; &#xB41C; &#xC720;&#xC804;&#xC790; predisposed &#xC6B0;&#xC6B8;&#xD55C; &#xBE44;&#xD5E4;&#xC774;&#xBE44;&#xC5B4;&#xB85C; Wistar &#xAD50;&#xD1A0; (WKY) &#xC950;&#xC5D0;&#xC11C; &#xC545;&#xD654;&#xB294; &#xB098;&#xD0C0;&#xB0AC;&#xB2E4;. &#xC2DC;&#xD504;, TMJ &#xC5FC;&#xC99D; nociceptive &#xD558;&#xD55C;&#xAC12; &#xB3D9;&#xC77C;&#xD55C; WKY &#xC950;&#xC5D0;&#xC11C; &#xC6B0;&#xC6B8;&#xC99D; &#xD589;&#xB3D9;&#xC758; &#xB354; &#xB192;&#xC740; &#xC810;&#xC218;&#xB97C; &#xC0C1;&#xD638; &#xC5F0;&#xAD00; &#xB418;&#xB3C4;&#xB85D; &#xC6B0;&#xC6B8;&#xD55C; &#xB3D9;&#xC791; &#xD5A5;&#xC0C1;. Wistar &#xC950;&#xC5D0; &#xBE44;&#xD574; WKY &#xC950; &#xB3D9;&#xCE21; trigeminal subnucleus caudalis (Sp5C)&#xC5D0; &#xC788;&#xB294; &#xB0AE;&#xC740; &#xD50C;&#xB77C;&#xC2A4;&#xB9C8; &#xBA5C; &#xB77C; &#xD1A0; &#xB2CC; &#xC218;&#xC900;, &#xBA5C; &#xB77C; &#xD1A0; &#xB2CC; MT1 &#xC218;&#xC6A9; &#xCCB4;&#xC758; downregulation &#xD558;&#xC9C0;&#xB9CC; NMDA &#xC218;&#xC6A9; &#xCCB4;&#xC758; NR1 &#xC18C; &#xB2E8;&#xC704;&#xC758; upregulation &#xBCF4;&#xC600;&#xB2E4;. 6-Chloromelatonin&#xC758; Intracisternal &#xAD00;&#xB9AC; (250&mu;g, 7 &#xC77C;&#xC744; &#xC704;&#xD574; &#xB9E4;&#xC77C; &#xB450; &#xBC88;) &#xB3D9;&#xC2DC;&#xC5D0; &#xAE30;&#xACC4;&#xC801; hyperalgesia&#xC640; WKY &#xC950; &#xC6B0;&#xC6B8;&#xD55C; &#xB3D9;&#xC791; &#xB3D9;&#xCE21; sp5c&#xC5D0; &#xC788;&#xB294; downregulated&#xB294; NR1 &#xC2DD; &#xAC10;&#xC1E0;. &#xD328;&#xCE58; &#xD074;&#xB7A8;&#xD504; &#xB179;&#xC74C;, &#xCC99;&#xC218; &#xB4F1; &#xCABD; &#xBFD4; substantia gelatinosa &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xC758; NMDA &#xC720;&#xBC1C; &#xC804;&#xB958; &#xAC10;&#xC18C; &#xBA5C; &#xB77C; &#xD1A0; &#xB2CC; &#xBCF5;&#xC6A9; &#xB3C5;&#xB9BD;&#xC801;. &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; TMJ &#xC5FC;&#xC99D; &#xC720;&#xBC1C; &#xAE30;&#xACC4; hyperalgesia&#xC640; &#xC6B0;&#xC6B8;&#xD55C; &#xD589;&#xB3D9; &#xAC04;&#xC758; &#xC0C1;&#xD638; &#xAD00;&#xACC4;&#xB97C; &#xC124;&#xBA85; &#xD558; &#xACE0; &#xC911;&#xC559; melatoninergic &#xC2DC;&#xC2A4;&#xD15C;&#xC758; NMDA &#xC218;&#xC6A9; &#xCCB4; &#xC2DD; &#xBC0F; &#xD65C;&#xB3D9;&#xC758; &#xBCC0;&#xC870;&#xB97C; &#xD1B5;&#xD574; &#xD1B5;&#xC99D;&#xACFC; &#xC6B0;&#xC6B8;&#xC99D; &#xC0AC;&#xC774;&#xC758; comorbidity &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC758; &#xC5ED;&#xD560;&#xC744; &#xD560; &#xC218; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC778;&#xD574; &#xAE30;&#xACC4;&#xC801; hyperalgesia &#xC950; &#xC720;&#xC804;&#xC790; predisposed &#xC6B0;&#xC6B8;&#xD55C; &#xB3D9;&#xC791;: &#xBA5C; &#xB77C; &#xD1A0; &#xB2CC; &#xBC0F; NMDA &#xC218;&#xC6A9; &#xCCB4;&#xC758; &#xC5ED;&#xD560;.

Una conexi&oacute;n entre el dolor y la depresi&oacute;n ha sido reconocida en el &aacute;mbito cl&iacute;nico; sin embargo, su mecanismo sigue siendo confuso. Este estudio mostr&oacute; hiperalgia mec&aacute;nica inducida por la inflamaci&oacute;n (ATM) de articulaci&oacute;n temporomandibular unilateral se agrav&oacute; en ratas Wistar-Kyoto (WKY) con comportamiento depresivo gen&eacute;ticamente predispuesto. Rec&iacute;procamente, inflamaci&oacute;n de TMJ hab&iacute;a mejorado comportamiento depresivo que una franquicia nociceptiva correlacionado con mayor puntaje de comportamiento depresivo en las mismas ratas WKY. En comparaci&oacute;n con ratas Wistar, ratas WKY demostraron un nivel inferior de melatonina plasm&aacute;tica, regulaci&oacute;n a la baja de los receptores de melatonina MT1, pero la regulaci&oacute;n al alza de la subunidad NR1 del receptor NMDA en el subnucleus trigeminal ipsolateral caudalis (Sp5C). Intracisternal administraci&oacute;n de 6-cloromelatonina (250&mu;g, dos veces al d&iacute;a por 7 d&iacute;as) simult&aacute;neamente aten&uacute;a hiperalgia mec&aacute;nica y comportamiento depresivo en ratas WKY, as&iacute; como expresi&oacute;n regulada la NR1 en el Sp5C ipsolateral. En grabaciones de patch-clamp, melatonina dosis dependiente disminuy&oacute; las corrientes inducidas por NMDA en neuronas de sustancia gelatinosa de cuerno dorsal de la m&eacute;dula espinal. Estos resultados demuestran una relaci&oacute;n rec&iacute;proca entre la Hiperalgesia mec&aacute;nica inducida por inflamaci&oacute;n de TMJ y comportamiento depresivo y sugieren que el sistema melatoninergic central, a trav&eacute;s de la modulaci&oacute;n de la expresi&oacute;n del receptor de NMDA y actividad, puede desempe&ntilde;ar un papel en los mecanismos de la comorbilidad entre depresi&oacute;n y dolor.

Hiperalgia mec&aacute;nica exacerbada en ratas con comportamiento depresivo predispuesto gen&eacute;ticamente: papel de la melatonina y los receptores NMDA.

To compare the patterns of respiratory function variations resulting from the classical reflex of blood pressure fall and high blood levels of bile acid, so as to provide evidence for the regulation of respiratory function via bile acids.

[Effect of high blood levels of bile acid on respiratory functions of New Zealand rabbits].

To observe changes in surface tension of bronchoalveolar lavage fluids (BALF) in rabbits with hyperbilirubinemia and the influence of bile diluents and 5 different bile acids on BALF surface tension to provide better insight into the regulatory role of bile acids on respiratory function.

[Effect of bile acids on surface tension of bronchoalveolar lavage fluid in rabbits].

Neuropathic pain and cognitive deficit are frequently comorbidity in clinical, but their underlying correlation and mechanisms remain unclear. Here, we utilized a combined rat model including kainic acid (KA) injection into bilateral striatal marginal division and chronic constriction nerve injury (CCI). PET/CT scans revealed that the SUVmax of KA rats was significantly decreased when compared to naive and saline rats. In contrast to the naive and saline rats, KA rats had longer latencies in locating the hidden platform on day 4, 5 in Morris water maze task. Thermal hyperalgesia and mechanical allodynia of KA rats were alleviated following CCI. Immunostaining results showed that substance P was markedly increased within ipsilateral spinal cord dorsal horn of KA rats after CCI, especially on the post-operative day 14. By means of real-time PCR, the up-regulation of GluR within ipsilateral spinal cord dorsal horn was observed in all KA and CCI rats. PKCγ, IL-6 and NF-κB were up-regulated in both CCI rats when compared to naive and their respective sham rats. These results suggest that cognitive impairment of rats altered the pain behaviors, and these intracellular regulators play crucial roles in the process of neuropathic pain. 

Effects on Spatial Cognition and Nociceptive Behavior Following Peripheral Nerve Injury in Rats with Lesion of the Striatal Marginal Division Induced by Kainic Acid.

Garcinia mangostana L. (Mangosteen) has been used to treat various pathological conditions, including inflammation and urinary tract infections. Here, we observed that garcinone D, a natural xanthone from mangosteen, promoted the proliferation of C17.2 neural progenitor cells and also resulted in a larger percentage of cells in S phase compared with the control group. Moreover, garcinone D increased the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and Cyclin D1 in concentration- and time- dependent manners. Garcinone D also increased the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in concentration- and time- dependent manners, and inhibiting Nrf2 activation by brusatol could partly reverse garcinone D-induced C17.2 cell proliferation. Taken together, it is the first time to show that garcinone D promotes the proliferation of C17.2 neural stem cells, which may involve the STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway. It would provide new inspiration to develop garcinone D as a lead compound to promote the proliferation of endogenous neural stem cells (NSCs).

Garcinone D, a natural xanthone promotes C17.2 neural stem cell proliferation: Possible involvement of STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway.

Objective. To determine whether bile acids (BAs) affect respiratory functions through the farnesoid X receptor (FXR) expressed in the lungs and to explore the possible mechanisms of BAs-induced respiratory disorder. Methods. Primary cultured alveolar epithelial type II cells (AECIIs) of rat were treated with different concentrations of chenodeoxycholic acid (CDCA) in the presence or absence of FXR inhibitor Z-guggulsterone (GS). Then, expression of FXR in nuclei of AECIIs was assessed by immunofluorescence microscopy. And ultrastructural changes of the cells were observed under transmission electron microscope and analyzed by Image-Pro Plus software. Results. Morphologic damage of AECIIs was exhibited in high BAs group in vitro, with high-level expression of FXR, while FXR inhibitor GS could attenuate the cytotoxicity of BAs to AECIIs. Conclusions. FXR expression was related to the morphologic damage of AECIIs induced by BAs, thus influencing respiratory functions. 

Morphologic Damage of Rat Alveolar Epithelial Type II Cells Induced by Bile Acids Could Be Ameliorated by Farnesoid X Receptor Inhibitor Z-Guggulsterone In Vitro.

Article	Year
Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain. Pain\| PubMed ID: 21376468	2011
Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: Role of melatonin and NMDA receptors. Pain\| PubMed ID: 23046768	2012
[Effect of high blood levels of bile acid on respiratory functions of New Zealand rabbits]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University\| PubMed ID: 23996762	2013
[Effect of bile acids on surface tension of bronchoalveolar lavage fluid in rabbits]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University\| PubMed ID: 25345943	2014
Effects on Spatial Cognition and Nociceptive Behavior Following Peripheral Nerve Injury in Rats with Lesion of the Striatal Marginal Division Induced by Kainic Acid. Neurochemical research\| PubMed ID: 26415594	2015
Garcinone D, a natural xanthone promotes C17.2 neural stem cell proliferation: Possible involvement of STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway. Neuroscience letters\| PubMed ID: 27177723	2016
Morphologic Damage of Rat Alveolar Epithelial Type II Cells Induced by Bile Acids Could Be Ameliorated by Farnesoid X Receptor Inhibitor Z-Guggulsterone In Vitro. BioMed research international\| PubMed ID: 27340672	2016

Yinghong Tian

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