mouse-short-long-term-locomotor-activity-analyzed-video-tracking

Mouse Short- and Long-term Locomotor Activity Analyzed by Video Tracking Software

Locomotor  activity (LMA) is a simple and easily performed measurement of behavior in mice  and other rodents. Improvements in video tracking software ...

University of Illinois at Urbana-Champaign

Acute hypoxia is experienced by a variety of individuals (neonates to the elderly) and in an assortment of conditions and diseases (terrorist bomb attack to decompensated heart failure). Increasingly, elaboration of inflammatory cytokines appears key to the brain-based response to hypoxia, as evidenced by the biobehaviors of malaise, fatigue, lethargy, and loss of interest in the physical and social environment. These sickness symptoms implicate hypoxia-dependent activation of the neuroimmune system as a key component of acute hypoxia. Type 2 diabetes (T2D) is associated with increased incidence, severity, and delayed recovery from hypoxic events. Why T2D negatively affects acute hypoxia is not well understood. Recent work, however, reveals that anti-inflammatory pathways tied to the interleukin (IL)-1beta arm of the neuroimmune system may be critical. In this review, the authors examine the link between acute hypoxia, T2D, and neuroimmunity.

Acute hypoxia, diabetes, and neuroimmune dysregulation: converging mechanisms in the brain.

L&#39;hypoxie aigu&euml; est connue par une vari&eacute;t&eacute; d&#39;individus (nouveaux-n&eacute;s aux personnes &acirc;g&eacute;es) et dans une vari&eacute;t&eacute; de conditions et maladies (attentat &agrave; la bombe terroriste &agrave; une insuffisance cardiaque d&eacute;compens&eacute;e). De plus en plus, &eacute;laboration des cytokines inflammatoires appara&icirc;t touche l&#39;ax&eacute;e sur le cerveau en r&eacute;ponse &agrave; l&#39;hypoxie, comme en t&eacute;moigne la biobehaviors de malaise, fatigue, l&eacute;thargie et perte d&#39;int&eacute;r&ecirc;t dans l&#39;environnement physique et social. Ces sympt&ocirc;mes de maladie impliquent activation hypoxie-d&eacute;pendante du syst&egrave;me neuro-immunitaire constitue un &eacute;l&eacute;ment cl&eacute; de l&#39;hypoxie aigu&euml;. Diab&egrave;te de type 2 (T2D) est li&eacute;e &agrave; l&#39;augmentation de la fr&eacute;quence, la gravit&eacute; et recouvrement diff&eacute;r&eacute; d&#39;&eacute;v&eacute;nements hypoxiques. Pourquoi T2D affecte n&eacute;gativement aigu&euml; l&#39;hypoxie n&#39;est pas bien comprise. Des travaux r&eacute;cents, cependant, r&eacute;v&egrave;lent que les anti-inflammatoires voies li&eacute;s &agrave; l&#39;interleukine (IL)-1beta bras du syst&egrave;me neuro-immunitaire peut &ecirc;tre critique. Dans cette revue, les auteurs examinent le lien entre une hypoxie aigu&euml;, T2D et neuroimmunity.

Dysr&eacute;gulation de l&#39;hypoxie, le diab&egrave;te et neuro-immunitaire aigu&euml; : m&eacute;canismes convergents dans le cerveau.

Ipossia acuta &egrave; sperimentato da una variet&agrave; di individui (i neonati agli anziani) e un assortimento di condizioni e malattie (attentato terroristico per insufficienza cardiaca scompensata). Sempre pi&ugrave;, elaborazione di citochine infiammatorie appare chiave per la risposta all&#39;ipossia, basata sul cervello come dimostra la biobehaviors del malessere, affaticamento, letargia e perdita di interesse per l&#39;ambiente fisico e sociale. Questi sintomi di malattia coinvolgono ipossia-dipendente dalla attivazione del sistema di neuroimmune come una componente chiave dell&#39;ipossia acuta. Diabete di tipo 2 (T2D) &egrave; associato con l&#39;aumento dell&#39;incidenza, gravit&agrave; e ritardato recupero da eventi ipossico. Perch&eacute; T2D lede acuta ipossia non &egrave; ben compreso. Lavori recenti, tuttavia, rivela che percorsi anti-infiammatori legato all&#39;interleuchina (IL)-1beta braccio del sistema del neuroimmune pu&ograve; essere critico. In questa revisione, gli autori esaminano il legame tra ipossia acuta, T2D e neuroimmunity.

Disregolazione del neuroimmune, il diabete e l&#39;ipossia acuta: meccanismi convergenti nel cervello.

Macrophages are capable of assuming numerous phenotypes in order to adapt to endogenous and exogenous challenges but many of the factors that regulate this process are still unknown. We report that Ca(2+)/calmodulin-dependent kinase kinase alpha (CaMKKalpha) is expressed in human monocytic cells and demonstrate that its inhibition blocks type-II monocytic cell activation and promotes classical activation. Affinity chromatography with paramagnetic beads isolated an approximately 50 kDa protein from nuclear lysates of U937 human monocytic cells activated with phorbol-12-myristate-13-acetate (PMA). This protein was identified as CaMKKalpha by mass spectrometry and Western analysis. The function of CaMKKalpha in monocyte activation was examined using the CaMKKalpha inhibitors (STO-609 and forskolin) and siRNA knockdown. Inhibition of CaMKKalpha, enhanced PMA-dependent CD86 expression and reduced CD11b expression. In addition, inhibition was associated with decreased translocation of CaMKKalpha to the nucleus. Finally, to further examine monocyte activation profiles, TNFalpha and IL-10 secretion were studied. CaMKKalpha inhibition attenuated PMA-dependent IL-10 production and enhanced TNFalpha production indicating a shift from type-II to classical monocyte activation. Taken together, these findings indicate an important new role for CaMKKalpha in the differentiation of monocytic cells.

Ca2+/calmodulin-dependent kinase kinase alpha is expressed by monocytic cells and regulates the activation profile.

Les macrophages sont capables d&#39;assumer de nombreux ph&eacute;notypes afin de s&#39;adapter aux d&eacute;fis endog&egrave;nes et exog&egrave;nes, mais bon nombre des facteurs qui r&eacute;gulent ce processus sont encore inconnues. Les auteurs rapportent qu&#39;alpha de kinase de kinase de Ca(2+)/calmoduline-d&eacute;pendante (CaMKKalpha) est exprim&eacute; dans les cellules humaines monocytaire et d&eacute;montrer que son inhibition bloque l&#39;activation des cellules monocytes type II et favorise l&#39;activation classique. Chromatographie d&#39;affinit&eacute; avec les billes paramagn&eacute;tiques isol&eacute; une prot&eacute;ine kDa environ 50 de nucl&eacute;aires lysats de cellules de monocytaire humaines U937 activ&eacute;s avec phorbol-12-myristate-13-ac&eacute;tate (PMA). Cette prot&eacute;ine a &eacute;t&eacute; identifi&eacute;e comme CaMKKalpha par spectrom&eacute;trie de masse et analyse occidentale. La fonction de CaMKKalpha dans l&#39;activation des monocytes a &eacute;t&eacute; &eacute;tudi&eacute;e en utilisant les inhibiteurs de la CaMKKalpha (STO-609 et la forskoline) et siRNA knockdown. L&#39;inhibition de la CaMKKalpha, am&eacute;lior&eacute;e PMA-d&eacute;pendante CD86 expression et r&eacute;duit CD11b expression. En outre, l&#39;inhibition a &eacute;t&eacute; associ&eacute;e &agrave; une diminution translocation de CaMKKalpha vers le noyau. Enfin, pour examiner davantage les profils d&#39;activation de monocytes, s&eacute;cr&eacute;tion de TNFalpha et d&#39;IL-10 ont &eacute;t&eacute; &eacute;tudi&eacute;s. CaMKKalpha inhibition att&eacute;nu&eacute;e PMA-d&eacute;pendant IL-10 production et am&eacute;lioration de la production TNFalpha indiquant un changement de type II &agrave; l&#39;activation des monocytes classique. Pris ensemble, ces r&eacute;sultats indiquent un r&ocirc;le nouveau et important pour CaMKKalpha dans la diff&eacute;renciation des cellules monocytes.

Ca2 + / kinase calmoduline-d&eacute;pendante kinase alpha est exprim&eacute; par les cellules monocytaire et r&eacute;glemente le profil d&#39;activation.

I macrofagi sono in grado di assumere numerosi fenotipi per adattarsi alle sfide endogene ed esogene, ma molti dei fattori che regolano questo processo sono ancora sconosciuti. Segnaliamo che alfa di chinasi della chinasi Ca(2+)/calmodulina-dipendente (CaMKKalpha) &egrave; espresso in cellule umane monocitica e dimostrare che la sua inibizione blocca l&#39;attivazione delle cellule monocitica tipo-II e promuove attivazione classica. La cromatografia di affinit&agrave; con perline paramagnetici isolata una proteina di circa 50 kDa da nucleare lisati di cellule monocitica umane U937 attivate con forbolo-12-Miristato-13-acetato (PMA). Questa proteina &egrave; stata identificata come CaMKKalpha di spettrometria di massa e analisi occidentale. La funzione di CaMKKalpha nell&#39;attivazione di monociti &egrave; stata esaminata usando gli inibitori CaMKKalpha (STO-609 e forskolina) e siRNA atterramento. Inibizione della CaMKKalpha, enhanced PMA-dipendente CD86 espressione e ridotta espressione CD11b. Inoltre, l&#39;inibizione &egrave; stato associato con diminuita traslocazione di CaMKKalpha nel nucleo. Infine, per esaminare ulteriormente i profili di attivazione monociti, secrezione TNFalpha e IL-10 sono stati studiati. CaMKKalpha inibizione attenuato IL PMA-dipendente-10 produzione e migliorata TNFalpha che indica un passaggio da tipo II ad attivazione monociti classica. Presi insieme, questi risultati indicano un ruolo nuovo per CaMKKalpha la differenziazione delle cellule monocitica.

Ca2 + calmodulina-dipendente della chinasi della chinasi alfa &egrave; espresso dalle cellule monocitica e regola il profilo di attivazione.

L&#39;hypoglyc&eacute;mie est associ&eacute; &agrave; une vari&eacute;t&eacute; de comportements ind&eacute;sirables, y compris la fatigue, confusion et retrait social. Bien que ces sympt&ocirc;mes cliniques sont bien caract&eacute;ris&eacute;s, le m&eacute;canisme de leur cause n&#39;est pas compris. Ici, nous avons &eacute;tudi&eacute; comment induite par l&#39;insuline hypoglyc&eacute;mie provoque le retrait social.

Blocage des r&eacute;cepteurs adr&eacute;nergiques b&ecirc;ta-2 acc&eacute;l&egrave;re la r&eacute;cup&eacute;ration de retrait social associ&eacute;es &agrave; l&#39;hypoglyc&eacute;mie.

L&#39;ipoglicemia &egrave; associato con una variet&agrave; di comportamenti negativi, tra cui stanchezza, confusione e ritiro sociale. Mentre questi sintomi clinici sono ben caratterizzati, non &egrave; compreso il meccanismo della loro causa. Qui abbiamo studiato l&#39;ipoglicemia insulino-indotta come causa ritiro sociale.

Blocco dei recettori adrenergici beta-2 accelera il recupero dall&#39;ipoglicemia associato al ritiro sociale.

Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal.

Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.

Individuals affected by hypoxia experience a variety of immune-associated sickness symptoms including malaise, fatigue, lethargy and loss of interest in the physical and social environment. Recently, we demonstrated that the interleukin (IL)-1beta arm of the neuroimmune system was critical to the sickness symptoms caused by hypoxia, and that IL-1 receptor antagonist (IL-1RA), IL-1beta's endogenous inhibitor, was critical to promoting sickness recovery. Here, we report that leptin is key to recovery from hypoxia because it dramatically augmented IL-1RA production in mice. We found that hypoxia increased leptin in white adipose tissue (WAT) which in turn, caused a marked rise in serum IL-1RA. Interestingly, in-vitro, leptin was a more potent inducer of IL-RA, in macrophages, than hypoxia. In leptin receptor defective (db/db) and leptin deficient (ob/ob) mice, sickness recovery from hypoxia was delayed 3-fold. Importantly, in ob/ob mice, leptin administration completely reversed this delayed recovery and induced a marked increase in serum IL-1RA. Finally, leptin administration to normal mice reduced hypoxia recovery time by 1/3 and dramatically increased WAT and serum IL-1RA. Leptin did not alter recovery from hypoxia in IL-1RA knock out mice. These results show that by enhancing IL-1RA production leptin promoted sickness recovery from hypoxia.

Behavioral recovery from acute hypoxia is reliant on leptin.

Personnes touch&eacute;es par l&#39;hypoxie &eacute;prouver une vari&eacute;t&eacute; de sympt&ocirc;mes de maladie immunitaire-associ&eacute;s dont le malaise, fatigue, l&eacute;thargie et perte d&#39;int&eacute;r&ecirc;t dans l&#39;environnement physique et social. R&eacute;cemment, nous avons montr&eacute; que l&#39;interleukine (IL)-1beta bras du syst&egrave;me neuro-immunitaire &eacute;tait critique pour les sympt&ocirc;mes de la maladie caus&eacute;es par l&#39;hypoxie, et cet antagoniste des r&eacute;cepteurs IL-1 (IL-1RA), inhibiteur endog&egrave;ne de IL-1beta, &eacute;tait essentiel pour promouvoir la valorisation de la maladie. Nous rapportons ici que la leptine est fondamental pour la r&eacute;cup&eacute;ration d&#39;hypoxie car il augment&eacute;e consid&eacute;rablement la production de IL-1RA chez la souris. Nous avons trouv&eacute; que l&#39;hypoxie a augment&eacute; de leptine dans le tissu adipeux blanc (WAT) qui &agrave; son tour, a provoqu&eacute; une augmentation marqu&eacute;e dans le s&eacute;rum, IL-1RA. Fait int&eacute;ressant, in vitro, la leptine a &eacute;t&eacute; un plus puissant inducteur de IL-RA, dans les macrophages, que l&#39;hypoxie. Dans le r&eacute;cepteur de la leptine d&eacute;fectueux (db/db) et souris carenc&eacute;es en leptine (ob/ob), r&eacute;cup&eacute;ration de la maladie de l&#39;hypoxie a &eacute;t&eacute; retard&eacute;e de 3 fois. Ce qui est important, chez les souris ob/ob, administration de leptine compl&egrave;tement invers&eacute; cette reprise retard&eacute;e et induit une augmentation marqu&eacute;e dans le s&eacute;rum, IL-1RA. Enfin, l&#39;administration de leptine &agrave; des souris normales r&eacute;duit temps de r&eacute;cup&eacute;ration de l&#39;hypoxie par 1/3 et une hausse ph&eacute;nom&eacute;nale WAT et s&eacute;rum IL-1RA. Leptine n&#39;alt&egrave;re pas la r&eacute;cup&eacute;ration de l&#39;hypoxie dans IL-1RA assommer de souris. Ces r&eacute;sultats montrent que, en am&eacute;liorant la production de IL-1RA leptine promu, r&eacute;cup&eacute;ration de la maladie de l&#39;hypoxie.

R&eacute;cup&eacute;ration comportementale de l&#39;hypoxie aigu&euml; est tributaire de la leptine.

Le persone affette da ipossia sperimentare una variet&agrave; di sintomi di malattia associata immunitario tra cui malessere, affaticamento, letargia e perdita di interesse per l&#39;ambiente fisico e sociale. Recentemente, abbiamo dimostrato che l&#39;interleuchina (IL)-1beta braccio del sistema del neuroimmune era fondamentale per i sintomi di malattia causati da ipossia e quello antagonista del recettore IL-1 (IL-1RA), inibitore endogeno del-1beta, fondamentale per promuovere la ripresa di malattia. Qui, segnaliamo che la leptina &egrave; chiave di recupero da ipossia perch&eacute; drammaticamente aumentata produzione di IL-1RA nei topi. Abbiamo trovato che l&#39;ipossia aumentati di leptina del tessuto adiposo bianco (WAT) che a sua volta, ha causato un aumento marcato nel siero IL-1RA. &Egrave; interessante notare che, in vitro, la leptina &egrave; stato un pi&ugrave; potente induttore di IL-RA, nei macrofagi, di ipossia. Leptin receptor difettoso (db/db) e topi (ob/ob) deficit di leptina, recupero di malattia da ipossia &egrave; stato ritardato 3 volte. Importante, nei topi ob/ob, leptina amministrazione completamente invertito questo recupero ritardato e indotta da un marcato aumento nel siero IL-1RA. Infine, somministrazione di leptina in topi normali ridotto tempo di recupero di ipossia da 1/3 e drammaticamente aumentato WAT e siero IL-1RA. La leptina non alterava recupero da ipossia in IL-1RA knock out topi. Questi risultati mostrano che, potenziando la produzione di IL-1RA leptina promosso recupero malattia da ipossia.

Recupero comportamentale da ipossia acuta &egrave; legata alla leptina.

In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (â‰¤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-Î± expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice.

The biobehavioral and neuroimmune impact of low-dose ionizing radiation.

Dans le contexte clinique, des expositions r&eacute;p&eacute;t&eacute;es (10-30) &agrave; faible doses de rayonnements ionisants (&le;200 cGy), comme on le voit en radioth&eacute;rapie pour le cancer, provoque la fatigue. Presque sait rien, cependant, la fatigue, induisant des effets d&#39;une exposition unique &agrave; environnementale faible dose des rayonnements ionisants qui pourraient se produire pendant le vol de haute altitude a&eacute;rien commercial, un accident de r&eacute;acteur nucl&eacute;aire ou un &eacute;v&eacute;nement de particules solaires (SPE). Pour &eacute;tudier l&#39;impact &agrave; court terme des radiations ionisantes faible dose sur la souris biobehaviors et neuroimmunity, souris CD-1 m&acirc;les ont &eacute;t&eacute; irradi&eacute; avec cGy 50 ou 200 cGy des rayonnements gamma ou proton tout le corps. Rayonnement gamma a &eacute;t&eacute; trouv&eacute; pour r&eacute;duire l&#39;activit&eacute; locomotrice spontan&eacute;e de 35 % et 36 %, respectivement, l&#39;irradiation apr&egrave;s 6 h. En revanche, le comportement motiv&eacute; d&#39;exploration sociale a &eacute;t&eacute; un-impacted par les rayons gamma. Examen de la transcription des g&egrave;nes des cytokines pro-inflammatoires dans le cerveau ont montr&eacute; que le rayonnement gamma augmentait hippocampe expression de TNF-&alpha;, d&egrave;s post-irradiation 4 h. C&#39;est coupl&eacute;e &agrave; des hausses subs&eacute;quentes IL-1RA (8 et 12 h apr&egrave;s irradiation) dans le cortex et l&#39;hippocampe et la diminution des activit&eacute;s associ&eacute;es au cytosquelette prot&eacute;ine r&eacute;gul&eacute;e (Arc) (irradiation de poste 24 h) dans le cortex. Enfin, le stress de retenue &eacute;tait un important modulateur de la r&eacute;ponse neuro-immune aux rayonnements bloquant la capacit&eacute; de 200 cGy gamma rayonnement portant atteinte &agrave; l&#39;activit&eacute; locomotrice et alt&eacute;rer la r&eacute;ponse inflammatoire &agrave; une irradiation, ax&eacute;e sur le cerveau. Pris ensemble, ces r&eacute;sultats indiquent que les rayonnements ionisants faible dose active rapidement le syst&egrave;me neuro-immunitaire, causant potentiellement des premiers sympt&ocirc;mes de fatigue comme apparition chez la souris.

L&#39;impact biobehavioral et neuro-immune des rayonnements ionisants &agrave; faible dose.

In ambito clinico, ripetute esposizioni (10-30) a basse dosi di radiazioni ionizzanti (&le;200 cGy), come si &egrave; visto in radioterapia per cancro, causa stanchezza. Quasi nulla si conosce, tuttavia, la fatica che inducono effetti di una singola esposizione ambientale radiazioni ionizzanti basso dosaggio che potrebbero verificarsi durante il volo aereo commerciale ad alta quota, un incidente del reattore nucleare o un evento di particelle solari (SPE). Per analizzare l&#39;impatto a breve termine delle radiazioni ionizzanti basso-dose sul mouse biobehaviors e neuroimmunity, CD-1 topi maschi sono stato irradiato con 50 cGy o 200 cGy di raggi gamma o protone tutto il corpo. Radiazione gamma &egrave; stato trovato per ridurre attivit&agrave; spontanea dell&#39;apparato locomotore del 35% e 36%, rispettivamente, irradiazione post 6 h. Al contrario, il comportamento motivato di esplorazione sociale era un-impacted da radiazioni gamma. Esame delle trascrizioni genica delle citochine pro-infiammatorie nel cervello hanno dimostrato che radiazioni gamma aumentata espressione di TNF-&alpha; hippocampal fin dal post-irradiation 4 h. Questo &egrave; stato accoppiato a successivi aumenti di IL-1RA (8 e 12 h post irradiazione) nell&#39;ippocampo e corteccia e riduzioni di attivit&agrave; regolamentate citoscheletro-associated protein (Arc) (irradiazione di post 24 h) nella corteccia. Infine, lo stress moderazione era un significativo modulatore della risposta neuroimmune alle radiazioni bloccando la capacit&agrave; di 200 cGy di raggi da ostacolando attivit&agrave; locomotorie e alterando la risposta infiammatoria basata sul cervello di irradiazione. Presi insieme, questi risultati indicano che radiazioni ionizzanti basso-dose attiva rapidamente il sistema di neuroimmune causando potenzialmente precoce insorgenza fatica-come i sintomi nei topi.

L&#39;impatto delle radiazioni ionizzanti basso-dose biocomportamentale e neuroimmune.

Use of individually ventilated caging (IVC) systems for mouse-based laboratory investigation has dramatically increased. We found that without mice present, intra-cage oxygen concentration was comparable (21%) between IVC housing and ambient environment caging (AEC) that used wire top lids. However, when mice were housed 4-to-a-cage for 1week, intra-cage oxygen dropped to 20.5% in IVC housing as compared to 21% for AEC housing. IVC intra-cage humidity was also elevated relative to AEC housing. Mice raised in IVC housing as compared to mice raised in AEC housing had higher RBC mass, hematocrit and hemoglobin concentrations. They also had elevated platelet counts but lower white blood cell counts. IVC mice, relative to AEC mice, had increased saccharin preference and increased fluid consumption but similar locomotion, food intake, social exploration and novel object recognition when tested in an AEC environment. Taken together, these data indicate that ventilated caging systems can have a 0.5% reduction from ambient oxygen concentration that is coupled to mouse red blood cell indices indicative of chronic exposure to a hypoxia. Importantly, IVC housing can impact behavioral testing for depressive-like behavior.

Individually ventilated cages cause chronic low-grade hypoxia impacting mice hematologically and behaviorally.

Utilisation de syst&egrave;mes de mise en cage individuelle ventil&eacute;e (IVC) pour enqu&ecirc;te ax&eacute;e sur les souris de laboratoire a consid&eacute;rablement augment&eacute;. Nous avons constat&eacute; que sans souris pr&eacute;sentes, concentration en oxyg&egrave;ne intra-cage &eacute;tait comparable (21 %) entre le logement de l&#39;IVC et environnement ambiant encagement couvercles (AEC) cette top du fil utilis&eacute;. Cependant, lorsque les souris &eacute;taient log&eacute; 4-&agrave;-un-cage pour 1 semaine, oxyg&egrave;ne intra-cage a chut&eacute; de 20,5 % dans le logement de IVC comparativement &agrave; 21 % pour le logement de l&#39;AEC. Humidit&eacute; intra-cage IVC &eacute;tait &eacute;galement &eacute;lev&eacute;e par rapport au logement de l&#39;AEC. Souris soulev&eacute;es dans le logement de IVC par rapport aux souris soulev&eacute;es dans le logement de l&#39;AEC avaient plus &eacute;lev&eacute; RBC de masse, les concentrations de l&#39;h&eacute;matocrite et l&#39;h&eacute;moglobine. Ils ont &eacute;galement &eacute;lev&eacute; des num&eacute;rations plaquettaires mais des lymphocytes de sang blanc inf&eacute;rieur. Souris IVC, par rapport &agrave; des souris de l&#39;AEC, avaient augment&eacute; de pr&eacute;f&eacute;rence de la saccharine et consommation de liquide mais locomotion semblable, la prise alimentaire, exploration sociale et reconnaissance d&#39;objets nouveaux lorsqu&#39;il est test&eacute; dans un environnement d&#39;AEC. Ensemble, ces donn&eacute;es indiquent que les syst&egrave;mes de mise en cage ventil&eacute;es peuvent avoir une r&eacute;duction de 0,5 % de la concentration d&#39;oxyg&egrave;ne qui est coupl&eacute;e aux indices de globules rouges de souris indicatives d&#39;une exposition chronique &agrave; une hypoxie. Ce qui est important, logement IVC peut avoir des r&eacute;percussions des tests comportementaux pour comportement d&eacute;pressif.

Cages individuellement ventil&eacute;es provoquent l&#39;hypoxie chronique bas grade impactant souris h&eacute;matologique et sur le plan comportemental.

Uso di sistemi individualmente ventilato ingabbiamento (IVC) per indagini di laboratorio basate sul mouse &egrave; aumentato drammaticamente. Abbiamo trovato che senza topi presenti, concentrazione di ossigeno intra-gabbia era paragonabile (21%) tra IVC alloggiamento e ambiente ambiente ingabbiamento coperchi (AEC) che top filo usato. Tuttavia, quando i topi erano alloggiato 4-a-a-gabbia per 1 settimana, ossigeno intra-gabbia &egrave; scesa al 20,5% in alloggiamento IVC rispetto al 21% per le abitazioni di AEC. Umidit&agrave; intra-gabbia IVC venne anche elevato rispetto alloggiamento AEC. Topi sollevati nell&#39;alloggiamento IVC rispetto ai topi sollevate nell&#39;alloggiamento AEC erano superiore RBC di massa, concentrazioni di ematocrito ed emoglobina. Hanno anche avuto elevata conta piastrinica ma conta inferiori di globuli bianchi. IVC topi, rispetto a topi AEC, avevano aumentato la preferenza di saccarina e aumentato consumo di liquido ma simile alla locomozione, assunzione di cibo, esplorazione sociale e riconoscimento oggetto romanzo quando testato in un ambiente di AEC. Presi insieme, questi dati indicano che sistemi di messa in gabbia ventilati possono avere una riduzione di 0,5% dalla concentrazione di ossigeno ambientale che &egrave; accoppiato a indici di globuli rossi del mouse indicativi dell&#39;esposizione cronica ad un&#39;ipossia. Soprattutto, alloggiamento IVC pu&ograve; avere un impatto test comportamentali per comportamenti simil-depressivi.

Gabbie individualmente ventilate causano ipossia cronica lieve impatto topi hematologically e comportamentale.

The field of psychoneuroimmunology (PNI) aims to uncover the processes and consequences of nervous, immune, and endocrine system relationships. Behavior is a consequence of such interactions and manifests from a complex interweave of factors including immune-to-neural and neural-to-immune communication. Often the signaling molecules involved during a particular episode of neuroimmune activation are not known but behavioral response provides evidence that bioactives such as neurotransmitters and cytokines are perturbed. Immunobehavioral phenotyping is a first-line approach when examining the neuroimmune system and its reaction to immune stimulation or suppression. Behavioral response is significantly more sensitive than direct measurement of a single specific bioactive and can quickly and efficiently rule in or out relevance of a particular immune challenge or therapeutic to neuroimmunity. Classically, immunobehavioral research was focused on sickness symptoms related to bacterial infection but neuroimmune activation is now a recognized complication of diseases and disorders ranging from cancer to diabesity. Immunobehaviors include lethargy, loss of appetite, and disinterest in social activity and the surrounding environment. In addition, neuroimmune activation can precipitate feelings of depression and anxiety while negatively impacting cognitive function and physical activity. Provided is a detailed overview of behavioral tests frequently used to examine neuroimmune activation in mice with a special emphasis on preexperimental conditions that can confound or prevent successful immunobehavioral experimentation.

Mouse testing methods in psychoneuroimmunology: an overview of how to measure sickness, depressive/anxietal, cognitive, and physical activity behaviors.

Le domaine de la psychoneuroimmunologie (PNI) a pour but de d&eacute;couvrir les processus et les cons&eacute;quences des relations du syst&egrave;me nerveux, immunitaire et endocrinien. Comportement est une cons&eacute;quence de ces interactions et manifestes d&#39;un entrelacs complexe de facteurs, notamment la communication immunitaire-&agrave;-neurale et neurones-&agrave;-immunitaires. Souvent les mol&eacute;cules de signalisation impliqu&eacute;es au cours d&#39;un &eacute;pisode particulier de neuro-immune activation ne sont pas connus mais la r&eacute;ponse comportementale apporte la preuve que compos&eacute;s bioactifs tels que les neurotransmetteurs et cytokines sont perturb&eacute;es. Immunobehavioral ph&eacute;notypage est une approche de premi&egrave;re ligne lorsqu&#39;il a examin&eacute; le syst&egrave;me neuro-immune et sa r&eacute;action &agrave; la stimulation immunitaire ou de la r&eacute;pression. R&eacute;ponse comportementale est nettement plus sensible que la mesure d&#39;une unique sp&eacute;cifique bioactif directe et peuvent rapidement et efficacement la r&egrave;gle dedans ou dehors la pertinence d&#39;un d&eacute;fi particulier immunitaire ou th&eacute;rapeutiques &agrave; neuroimmunity. Classiquement, immunobehavioral s&#39;int&eacute;ressait particuli&egrave;rement &agrave; des sympt&ocirc;mes de maladie li&eacute;es &agrave; une infection bact&eacute;rienne mais activation neuro-immune est une complication reconnue des maladies et des troubles allant du cancer &agrave; la diab&eacute;sit&eacute;. Immunobehaviors incluent l&eacute;thargie, perte d&#39;app&eacute;tit et d&eacute;sint&eacute;r&ecirc;t dans l&#39;activit&eacute; sociale et le milieu environnant. En outre, neuro-immune activation peut pr&eacute;cipiter les sentiments de d&eacute;pression et d&#39;anxi&eacute;t&eacute; tout en impactant n&eacute;gativement la fonction cognitive et l&#39;activit&eacute; physique. A fourni un aper&ccedil;u d&eacute;taill&eacute; des tests comportementaux est fr&eacute;quemment utilis&eacute; pour examiner l&#39;activation neuro-immunitaire chez des souris avec un accent particulier sur les conditions preexperimental qui peut confondre ou pr&eacute;venir l&#39;exp&eacute;rimentation r&eacute;ussie d&#39;immunobehavioral.

M&eacute;thodes de test en psychoneuroimmunologie de souris : un aper&ccedil;u de la fa&ccedil;on de mesurer la maladie, d&eacute;pressif/anxietal, cognitif et des comportements de l&#39;activit&eacute; physique.

Il campo di psychoneuroimmunology (PNI) mira a scoprire i processi e le conseguenze dei rapporti del sistema nervoso, sistema immunitario e sistema endocrino. Il comportamento &egrave; una conseguenza di tali interazioni e manifesti da un complesso intreccio di fattori tra cui comunicazione immunitaria-neurale e neurali--immune. Spesso non si conoscono le molecole di segnalazione coinvolte durante un particolare episodio del neuroimmune attivazione ma risposta comportamentale fornisce la prova che bioactives come neurotrasmettitori e citochine sono perturbate. Immunobehavioral fenotipi sono un approccio di prima linea quando si esamina il sistema del neuroimmune e la sua reazione alla stimolazione del sistema immunitaria o soppressione. Risposta comportamentale &egrave; significativamente pi&ugrave; sensibile rispetto diretta misurazione di un singolo specifico bioattivo e pu&ograve; rapidamente ed efficientemente la regola dentro o fuori la pertinenza di una particolare sfida immune o terapeutico a neuroimmunity. Classicamente, immunobehavioral ricerca era focalizzata sui sintomi di malattia correlati all&#39;infezione batterica, ma l&#39;attivazione di neuroimmune ora &egrave; una complicazione riconosciuta di malattie e disturbi che vanno dal cancro di diabesity. Immunobehaviors includono letargia, perdita di appetito e il disinteresse in attivit&agrave; sociale e l&#39;ambiente circostante. Inoltre, neuroimmune attivazione pu&ograve; scatenare sentimenti di depressione e ansia durante un impatto negativo la funzione cognitiva e l&#39;attivit&agrave; fisica. Fornito &egrave; una panoramica dettagliata dei test comportamentali frequentemente utilizzata per esaminare neuroimmune attivazione nei topi con una particolare attenzione alle condizioni preexperimental che possono confondere o prevenire la sperimentazione di successo immunobehavioral.

Metodi di prova in psychoneuroimmunology il mouse: una panoramica di come misurare la malattia, depressivo/anxietal, cognitivi e comportamenti di attivit&agrave; fisica.

The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1-3wks) of a high-fat diet (HFD). After 1wk of a HFD feeding, mouse burrowing and spontaneous wheel running were increased while mouse exploration of the open quadrants of a zero maze, perfect alternations in a Y-maze and recognition of a novel object were impaired. Examination of mouse cortex, hippocampus and hypothalamus for dopamine and its metabolites demonstrated increased homovanillic acid (HVA) concentrations in the hippocampus and cortex that were associated with decreased cortical BDNF gene expression. In contrast, pro-inflammatory cytokine gene transcripts and serum IL-1Î±, IL-1Î², TNF-Î± and IL-6 were unaffected by the short-term HFD feeding. Administration to mice of the psychostimulant methylphenidate prevented HFD-dependent impairment of learning/memory. HFD learning/memory impairment was not inhibited by the anti-depressants desipramine or reboxetine nor was it blocked in IDO or IL-1R1 knockout mice. In sum, a HFD rapidly impacts dopamine metabolism in the brain appearing to trigger anxiety-like behaviors and learning/memory impairments prior to the onset of weight gain and/or pre-diabetes. Thus, overnutrition due to fats may be central to childhood psychological perturbations such as anxiety and ADHD.

Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice.

La pr&eacute;valence de l&#39;ob&eacute;sit&eacute; infantile a augment&eacute; de fa&ccedil;on spectaculaire et qui co&iuml;ncide avec cette recrudescence est une croissance en conditions psychologiques n&eacute;fastes de l&#39;enfance, y compris la d&eacute;pression, l&#39;impulsivit&eacute;, l&#39;anxi&eacute;t&eacute; et trouble hyperactif/d&eacute;ficit de l&#39;attention (TDAH). En raison de qui confond existent lors de la d&eacute;termination de la causalit&eacute; des perturbations comportementales de l&#39;enfance, controverse demeure quant &agrave; savoir si l&#39;ob&eacute;sit&eacute; surnutrition et/ou de l&#39;enfance est importante. Par cons&eacute;quent, nous avons examin&eacute; les souris juv&eacute;niles afin de d&eacute;terminer si les biobehaviors ont &eacute;t&eacute; touch&eacute;s par une alimentation &agrave; court terme (1 &agrave; 3 semaines) d&#39;une alimentation riche en graisses (HFD). Apr&egrave;s une semaine d&#39;une alimentation de HFD, souris fouisseurs et fonctionnement de rad spontan&eacute;e ont augment&eacute; tandis que l&#39;exploration de souris des quadrants ouvertes d&#39;un labyrinthe de z&eacute;ro, des alternances parfaits dans un labyrinthe en Y et la reconnaissance d&#39;un nouvel objet ont &eacute;t&eacute; alt&eacute;r&eacute;es. Examen de cortex de souris, hippocampe et l&#39;hypothalamus pour la dopamine et ses m&eacute;tabolites ont d&eacute;montr&eacute; homovanillique une augmentation des concentrations d&#39;acide (HVA) dans l&#39;hippocampe et le cortex qui &eacute;taient associ&eacute;es &agrave; une diminution corticale expression g&eacute;nique BDNF. En contraste, la transcription des g&egrave;nes des cytokines pro-inflammatoires et le s&eacute;rum IL-1&alpha;, IL-1&beta;, TNF-&alpha; et IL-6 ne sont pas affect&eacute;s par l&#39;alimentation &agrave; court terme de HFD. Administration &agrave; des souris de la m&eacute;thylph&eacute;nidate psychostimulant emp&ecirc;ch&eacute; d&eacute;pr&eacute;ciation de HFD-d&eacute;pendante d&#39;apprentissage/m&eacute;moire. Apprentissage/mn&eacute;sique de HFD n&#39;est pas inhib&eacute;e par la d&eacute;sipramine anti-d&eacute;presseurs ou reboxetine ni est elle bloqu&eacute;e en IDO ou IL-1R1 souris knock-out. En somme, un HFD impacts rapidement du m&eacute;tabolisme de la dopamine dans le cerveau qui appara&icirc;t pour d&eacute;clencher des comportements de type anxi&eacute;t&eacute; et troubles d&#39;apprentissage/m&eacute;moire avant le d&eacute;but de la prise de poids et/ou de pr&eacute;-diab&egrave;te. Ainsi, surnutrition due &agrave; graisses peut &ecirc;tre centrale aux perturbations psychologiques de l&#39;enfance comme l&#39;anxi&eacute;t&eacute; et le TDAH.

M&eacute;thylph&eacute;nidate emp&ecirc;che l&#39;alimentation riche en graisses (HFD)-induite d&#39;apprentissage/mn&eacute;sique chez les jeunes souris.

La prevalenza dell&#39;obesit&agrave; infantile &egrave; aumentato drammaticamente e coincida con questo aumento &egrave; una crescita in condizioni psicologiche avverse infanzia impulsivit&agrave;, depressione, ansia e disordine iperattivit&agrave;/deficit di attenzione (ADHD). A causa di che confonde esiste quando si determina la causalit&agrave; delle perturbazioni del comportamento infantile, polemica rimane come se overnutrition e/o infanzia obesit&agrave; &egrave; importante. Pertanto, abbiamo esaminato giovanili topi per determinare se biobehaviors sono stati influenzati da un&#39;alimentazione a breve termine (1-3 sett) di una dieta ad alto contenuto di grassi (HFD). Dopo 1 settimana di un&#39;alimentazione HFD, mouse scavatori e spontanea della rotella sono stati aumentati durante l&#39;esplorazione del mouse dei quadranti aperti di un labirinto zero, alternanze perfetti in una Y-labirinto e il riconoscimento di un oggetto romanzo sono stati alterati. Esame della corteccia del mouse, ippocampo ed ipotalamo per dopamina e dei suoi metaboliti ha dimostrato maggiore omovanilico acid (HVA) concentrazioni nell&#39;ippocampo e la corteccia che sono state associate con ridotta espressione del gene BDNF corticale. In contrasto, le trascrizioni di gene di citochine pro-infiammatorie e siero IL-1&alpha;, IL-1 &beta;, TNF-&alpha; e IL-6 sono state influenzate dall&#39;alimentazione HFD a breve termine. Somministrazione a topi del metilfenidato psicostimolante impedito danno HFD-dipendente della memoria/apprendimento. Compromissione di memoria/apprendimento HFD non era inibito la desipramina anti-depressivi o Reboxetina, n&eacute; &egrave; stato bloccato in IDO o IL-1R1 topi knockout. In somma, un HFD impatti rapidamente il metabolismo della dopamina nel cervello che appaiono per innescare comportamenti simil-ansia e disturbi della memoria/apprendimento prima dell&#39;inizio dell&#39;aumento di peso e/o pre-diabete. Cos&igrave;, overnutrition a causa di grassi pu&ograve; essere centrale alle perturbazioni psicologiche infanzia come ansia e ADHD.

Il metilfenidato impedisce la dieta ad alta percentuale di grassi (HFD)-indotta da compromissione della memoria/apprendimento nei topi giovanili.

Obesity is characterized by the presence of chronic inflammation in adipose tissue, particularly in the visceral compartment, that has been causally linked to development of obesity-associated comorbidities. This link can be either direct or indirect, through induction of insulin resistance. This review summarizes recent evidence on potential pharmacological targets of adipose tissue inflammation, with emphasis on mediators that are being studied for intervention in chronic inflammatory diseases and are therefore viable therapeutical candidates. Specifically, we discuss evidence on the role of the inflammasome and its downstream products as a potential target for anti-inflammatory strategies as well as T regulatory (Treg) cells and mediators involved in the resolution phase of inflammation such as resolvins, protectins, annexin A1 (ANXA1) and galectins as potential targets for novel agonist therapies.

New pathways to control inflammatory responses in adipose tissue.

L&#39;ob&eacute;sit&eacute; est caract&eacute;ris&eacute;e par la pr&eacute;sence d&#39;une inflammation chronique dans le tissu adipeux, notamment dans le compartiment visc&eacute;ral, qui a &eacute;t&eacute; directement li&eacute; au d&eacute;veloppement des comorbidit&eacute;s associ&eacute;es &agrave; l&#39;ob&eacute;sit&eacute;. Ce lien peut &ecirc;tre direct ou indirect, par induction de r&eacute;sistance &agrave; l&#39;insuline. Cette revue r&eacute;sume les donn&eacute;es r&eacute;centes sur les cibles pharmacologiques potentielles d&#39;inflammation du tissu adipeux, en mettant l&#39;accent sur les m&eacute;diateurs qui sont &agrave; l&#39;&eacute;tude d&#39;intervention dans les maladies inflammatoires chroniques et sont donc des candidats th&eacute;rapeutiques viables. Plus pr&eacute;cis&eacute;ment, nous discutons des preuves sur le r&ocirc;le de l&#39;inflammasome et ses produits en aval comme une cible potentielle pour des strat&eacute;gies anti-inflammatoires ainsi que r&eacute;glementaires (Treg) cellules de T et m&eacute;diateurs impliqu&eacute;s dans la phase de r&eacute;solution de l&#39;inflammation tels que r&eacute;solvines, protectins, annexine A1 (ANXA1) et galectines comme des cibles potentielles pour des th&eacute;rapies de nouveaux agonistes.

Jason M. York

Department of Animal Sciences

University of Illinois at Urbana-Champaign

Mouse Short- and Long-term Locomotor Activity Analyzed by Video Tracking Software