|Presentation||Lyophilized. Buffer = 0.01 M Sodium Phosphate, 0.25 M NaCl, pH 7.6 with 15 mg/mL BSA, and 0.05% sodium azide.
Reconstitute with 500 μL of sterile distilled water.
|Specificity||Specific for Goat IgG.|
|Antibody Type||Polyclonal Antibody|
|Purification Method||Immunoaffinity Purified and Immunodepletion|
|Safety Information according to GHS|
|Material Size||500 µL|
References | 18 Available | See All References
|Reference overview||Application||Pub Med ID|
|Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development. |
Shamis, Y; Cullen, DE; Liu, L; Yang, G; Ng, SF; Xiao, L; Bell, FT; Ray, C; Takikawa, S; Moskowitz, IP; Cai, CL; Yang, X; Li, X
Proceedings of the National Academy of Sciences of the United States of America 112 E2020-9 2015
Zfp57 is a maternal-zygotic effect gene that maintains genomic imprinting. Here we report that Zfp57 mutants exhibited a variety of cardiac defects including atrial septal defect (ASD), ventricular septal defect (VSD), thin myocardium, and reduced trabeculation. Zfp57 maternal-zygotic mutant embryos displayed more severe phenotypes with higher penetrance than the zygotic ones. Cardiac progenitor cells exhibited proliferation and differentiation defects in Zfp57 mutants. ZFP57 is a master regulator of genomic imprinting, so the DNA methylation imprint was lost in embryonic heart without ZFP57. Interestingly, the presence of imprinted DLK1, a target of ZFP57, correlated with NOTCH1 activation in cardiac cells. These results suggest that ZFP57 may modulate NOTCH signaling during cardiac development. Indeed, loss of ZFP57 caused loss of NOTCH1 activation in embryonic heart with more severe loss observed in the maternal-zygotic mutant. Maternal and zygotic functions of Zfp57 appear to play redundant roles in NOTCH1 activation and cardiomyocyte differentiation. This serves as an example of a maternal effect that can influence mammalian organ development. It also links genomic imprinting to NOTCH signaling and particular developmental functions.
|Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area neurons that project to the medial prefrontal cortex. |
Del Cid-Pellitero, E; Garzón, M
BMC neuroscience 15 105 2014
Hypocretins/orexins (Hcrt/Ox) are hypothalamic neuropeptides involved in sleep-wakefulness regulation. Deficiency in Hcrt/Ox neurotransmission results in the sleep disorder narcolepsy, which is characterized by an inability to maintain wakefulness. The Hcrt/Ox neurons are maximally active during wakefulness and project widely to the ventral tegmental area (VTA). A dopamine-containing nucleus projecting extensively to the cerebral cortex, the VTA enhances wakefulness. In the present study, we used retrograde tracing from the medial prefrontal cortex (mPFC) to examine whether Hcrt1/OxA neurons target VTA neurons that could sustain behavioral wakefulness through their projections to mPFC.The retrograde tracer Fluorogold (FG) was injected into mPFC and, after an optimal survival period, sections through the VTA were processed for dual immunolabeling of anti-FG and either anti-Hcrt1/OxA or anti-TH antisera. Most VTA neurons projecting to the mPFC were located in the parabrachial nucleus of the ipsilateral VTA and were non-dopaminergic. Only axonal profiles showed Hcrt1/OxA-immunoreactivity in VTA. Hcrt1/OxA reactivity was observed in axonal boutons and many unmyelinated axons. The Hcrt1/OxA immunoreactivity was found filling axons but it was also observed in parts of the cytoplasm and dense-core vesicles. Hcrt1/OxA-labeled boutons frequently apposed FG-immunolabeled dendrites. However, Hcrt1/OxA-labeled boutons rarely established synapses, which, when they were established, were mainly asymmetric (excitatory-type), with either FG-labeled or unlabeled dendrites.Our results provide ultrastructural evidence that Hcrt1/OxA neurons may exert a direct synaptic influence on mesocortical neurons that would facilitate arousal and wakefulness. The paucity of synapses, however, suggest that the activity of VTA neurons with cortical projections might also be modulated by Hcrt1/OxA non-synaptic actions. In addition, Hcrt1/OxA could modulate the postsynaptic excitatory responses of VTA neurons with cortical projections to a co-released excitatory transmitter from Hcrt1/OxA axons. Our observation of Hcrt1/OxA targeting of mesocortical neurons supports Hcrt1/OxA wakefulness enhancement in the VTA and could help explain the characteristic hypersomnia present in narcoleptic patients.
|Expression of hepatocyte epidermal growth factor receptor, FAS and glypican 3 in EpCAM-positive regenerative clusters of hepatocytes, cholangiocytes, and progenitor cells in human liver failure. |
Hattoum, A; Rubin, E; Orr, A; Michalopoulos, GK
Human pathology 44 743-9 2013
Liver regeneration under normal circumstances proceeds through proliferation of all cellular elements of the liver. Studies with rodent models have shown that when proliferation of hepatocytes is inhibited, progenitor cells arising from the biliary compartment transdifferentiate into "oval/progenitor" cells, which proceed to differentiate into hepatocytes. Recent studies have shown that the same pathways may operate in human liver failure. The growth factor receptors (HGF [hepatocyte growth factor] receptor) and epidermal growth factor receptor are key mitogenic receptors for both hepatocytes and progenitor cells. Our current study used the biliary and progenitor marker EpCAM (epithelial cell adhesion molecule) to detect "regenerative clusters" of mixed cholangiocyte-hepatocyte differentiation. We determined that expression of metabolic equivalent and epidermal growth factor receptor occurs in biliary cells, progenitor cells, and hepatocytes, whereas activation of metabolic equivalent and epidermal growth factor receptor is limited to regenerative cluster hepatocytes. These histologic events are associated with expression of apoptosis-inducing FAS and mitoinhibitory protein glypican 3. Cell proliferation was overall suppressed in regenerative clusters. Transdifferentiation of biliary and progenitor cells appears to be regulated by a complex interaction of signals promoting and arresting growth.
|Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment. |
Yetman, MJ; Jankowsky, JL
The Journal of neuroscience : the official journal of the Society for Neuroscience 33 17335-41 2013
Adult neurogenesis is modulated by a balance of extrinsic signals and intrinsic responses that maintain production of new granule cells in the hippocampus. Disorders that disrupt the proliferative niche can impair this process, and alterations in adult neurogenesis have been described in human autopsy tissue and transgenic mouse models of Alzheimer's disease. Because exogenous application of aggregated Aβ peptide is neurotoxic in vitro and extracellular Aβ deposits are the main pathological feature recapitulated by mouse models, cell-extrinsic effects of Aβ accumulation were thought to underlie the breakdown of hippocampal neurogenesis observed in Alzheimer's models. We tested this hypothesis using a bigenic mouse in which transgenic expression of APP was restricted to mature projection neurons. These mice allowed us to examine how wild-type neural progenitor cells responded to high levels of Aβ released from neighboring granule neurons. We find that the proliferation, determination, and survival of hippocampal adult-born granule neurons are unaffected in the APP bigenic mice, despite abundant amyloid pathology and robust neuroinflammation. Our findings suggest that Aβ accumulation is insufficient to impair adult hippocampal neurogenesis, and that factors other than amyloid pathology may account for the neurogenic deficits observed in transgenic models with more widespread APP expression.
|Long-term exercise is a potent trigger for ΔFosB induction in the hippocampus along the dorso-ventral axis. |
Nishijima, T; Kawakami, M; Kita, I
PloS one 8 e81245 2013
Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso-ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise-induced hippocampal plasticity.
|Scaffolds containing growth factors and extracellular matrix induce hepatocyte proliferation and cell migration in normal and regenerating rat liver. |
Hammond JS, Gilbert TW, Howard D, Zaitoun A, Michalopoulos G, Shakesheff KM, Beckingham IJ, Badylak SF.
Journal of hepatology 54 279-87 2011
Intrahepatic drug delivery from implantable scaffolds is being developed as a strategy to modulate growth and enhance regeneration at the time of liver resection. In this study we examine the effects of scaffolds containing hepatocyte growth factor, epidermal growth factor, fibroblast growth factor 1, fibroblast growth factor 2, and liver-derived extracellular matrix (L-ECM) when implanted into normal and partially hepatectomized rat livers.
|Hypocretin1/OrexinA axon targeting of laterodorsal tegmental nucleus neurons projecting to the rat medial prefrontal cortex. |
Cid-Pellitero, Ed; Garzón, M
Cerebral cortex (New York, N.Y. : 1991) 21 2762-73 2011
Cortical activation and goal-directed behaviors characterize wakefulness. One cortical region especially involved in these phenomena is the medial prefrontal cortex (mPFC), which receives many inputs from cholinergic-containing neurons in brain stem structures implicated in arousal and wakefulness, such as the laterodorsal tegmental nucleus (LDT). Hypocretins/orexins (Hcrt/Ox), whose dysfunction is linked to narcolepsy, maintains arousal and stabilizes sleep-wakefulness states. We aim to determine if Hcrt1/OxA axons (1) innervate LDT neurons projecting to the mPFC, a target that would allow them to sustain arousal and wakefulness, and (2) target preferentially cholinergic versus noncholinergic LDT neurons. The retrograde tracer Fluorogold (FG) was injected in the rat mPFC, and dual immunolabeling of anti-FG and either anti-choline acetyltransferase (ChAT) or anti-Hcrt1/OxA antisera was determined in LDT. Also, actual Hcrt1/OxA targeting of cholinergic LDT neurons was ascertained by dual anti-Hcrt1/OxA and anti-ChAT detection in additional noninjected animals. Many LDT FG-labeled neurons were cholinergic (52.05 ± 3.72%). Hcrt1/OxA immunoprecipitate was observed in cytoplasm and granular vesicles within axons. Some Hcrt1/OxA-containing axons established asymmetric excitatory-type synapses with either unlabeled (46/438) or FG-labeled (7/438) dendrites. One-third of the target neurons were ChAT labeled. Hcrt1/OxA excitatory input to LDT neurons projecting to mPFC probably contributes to the wakefulness-enhancing actions of Hcrt/Ox impaired in narcoleptics.
|Medial prefrontal cortex receives input from dorsal raphe nucleus neurons targeted by hypocretin1/orexinA-containing axons. |
E Del Cid-Pellitero,M Garzón
Neuroscience 172 2011
The medial prefrontal cortex (mPFC) is strongly involved in cognition and behavior. It receives input from brainstem nuclei implicated in behavioral wakefulness and electrographic cortical activation, such as the dorsal raphe nucleus (DRN). Moreover, the hypocretinergic/orexinergic (Hcrt/Ox) hypothalamic neurons innervate DRN, thus modulating its activity and presumably allowing transitions between sleep-wakefulness cycle states. Dysfunction in this system is associated with narcolepsy. In this study we aimed to determine the precise location of DRN neurons projecting to mPFC and the extent to which they contain serotonin (5-hydroxytryptamine); we have also assessed whether Hcrt1/OxA neurons innervate DRN neurons that could sustain behavioral wakefulness through their projections to mPFC. The retrograde tracer Fluorogold was injected into mPFC and DRN sections were processed for double immunolabeling of anti-Fluorogold and either anti-5-hydroxytryptamine or anti-Hcrt1/OxA antisera. Most DRN neurons projecting to mPFC were located in the ventral sector of the rostral and intermediate DRN, and around half of them were serotonergic. Hcrt1/OxA-immunoreactivity in DRN was observed in unmyelinated axons and axon boutons (varicosities or axon terminals). Hcrt1/OxA immunoreactivity was observed within the cytoplasm and in dense-cored vesicles of these axons. Hcrt1/OxA-labeled boutons established both asymmetric synapses (n=30) and appositional contacts (n=102) with Fluorogold-labeled dendrites belonging to DRN neurons projecting to mPFC. Our results show that Hcrt1/OxA neurons may exert a direct synaptic influence on DRN neurons that could facilitate wakefulness, although other non-synaptic actions through volume transmission are also suggested.
|Hypocretin1OrexinA-containing axons innervate locus coeruleus neurons that project to the rat medial prefrontal cortex. Implication in the sleep-wakefulness cycle and cortical activation. |
Cid-Pellitero ED, Garzón M
The Hypocretin1/OrexinA (Hcrt1/OxA) neuropeptides are found in a group of posterolateral hypothalamus neurons and are involved in sleep-wakefulness cycle regulation. Hcrt1/OxA neurons project widely to brainstem aminergic structures, such as the locus coeruleus (LC), which are involved in maintenance of wakefulness and EEG activation through intense projections to the medial prefrontal cortex (mPFC). Moreover, defects of the Hcrt1/OxA system are linked to narcolepsy, a disorder characterized by excessive diurnal hypersomnia and REM state disturbance. We aimed to determine whether Hcrt1/OxA neurons innervate LC neurons (noradrenergic and nonnoradrenergic) that project to the mPFC, thereby sustaining behavioral wakefulness. To assess this, we used retrograde tracing from mPFC injections and either Hcrt1/OxA or tyrosine hydroxylase (TH) immunohistochemical labeling in single sections of rat LC. The retrograde tracer Fluorogold (FG) was microinjected into mPFC and, at optimal survival periods, sections through the LC were processed for dual immunolabeling of anti-FG and either anti-Hcrt1/OxA or anti-TH antisera. Many LC neurons projecting to mPFC were nonnoradrenergic. Electron microscopy revealed a prominent localization of Hcrt1/OxA in unmyelinated axons and axon boutons (varicosities and axon terminals) within the LC. Hcrt1/OxA-immunoreactive axon boutons frequently apposed (104/1907) or made asymmetric excitatory-type synapses (60/1907) with FG-immunolabeled dendrites, indicating that Hcrt1/OxA can modulate the activity of LC neurons with cortical projections. Our results show that Hcrt1/OxA hypothalamic neurons likely excite LC neurons that project to the mPFC, and thus activate EEG and facilitate wakefulness. In narcoleptics, who are deficient in Hcrt1/OxA, impairment of this Hcrt1/OxA hypothalamic input to LC might contribute to the appearance of excessive daytime sleepiness. Synapse , 2011. © 2011 Wiley-Liss, Inc.Copyright © 2011 Wiley-Liss, Inc.
|Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. |
Cowden, JM; Riley, JP; Ma, JY; Thurmond, RL; Dunford, PJ
Respiratory research 11 86 2010
Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H4 receptor (H4R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H4R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH), and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined.Mice were sensitized to ovalbumin (OVA) followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H4R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR) was measured, lungs lavaged and tissues collected for analysis.Therapeutic H4R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H4R antagonist also improved measures of central and peripheral airway dysfunction.These data demonstrate that therapeutic H4R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H4R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.
|Increased COX2 in the trigeminal nucleus caudalis is involved in orofacial pain induced by experimental tooth movement. |
Yuan Gao,Yin-Zhong Duan
Anatomical record (Hoboken, N.J. : 2007) 293 2010
Pain is among the major problems during orthodontic treatment. Recent studies have shown that central Cyclooxygenase2 (COX2) pathway was involved in several pain models. The present study investigated whether inducible COX2 within the trigeminal nucleus caudalis (Vc) contributed to experimental tooth movement pain in freely moving rats. Elastic rubber bands were inserted between the first and second maxillary molars bilaterally to establish tooth movement model. The directed mouth wiping behavior was used to evaluate the pain during tooth movement. COX2 distribution in Vc was studied by immunohistochemistry and the changes of COX2 expression were detected by Western blot at different time point after rubber band insertion. Our results showed that tooth movement significantly increased COX2 expression in Vc and the time spent on mouth wiping, reaching a maximum at 1 day and then decreasing gradually. Furthermore, the rhythm change of COX2 expression in Vc and the mouth wiping behavior were much correlative with each other. All of the COX2-immunoreactive structures in Vc exhibited NeuN-immunopositive staining and most of these COX2-immunoreactive neurons were Fos-immunopositive. Importantly, the mouth wiping behavior could be attenuated by intracisternal injection of NS-398 (a selective COX2 inhibitor) but not by periodontal administration of NS-398. All these results suggested that increased COX2 in Vc was involved in tooth movement pain and thus may be a central target for orthodontic pain treatment.
|Coexpression of VGLUT1 and VGLUT2 in trigeminothalamic projection neurons in the principal sensory trigeminal nucleus of the rat. |
Shun-Nan Ge,Yun-Fei Ma,Hiroyuki Hioki,Yan-Yan Wei,Takeshi Kaneko,Noboru Mizuno,Guo-Dong Gao,Jin-Lian Li
The Journal of comparative neurology 518 2010
VGLUT1 and VGLUT2 have been reported to show complementary distributions in most brain regions and have been assumed to define distinct functional elements. In the present study, we first investigated the expression of VGLUT1 and VGLUT2 in the trigeminal sensory nuclear complex of the rat by dual-fluorescence in situ hybridization. Although VGLUT1 and/or VGLUT2 mRNA signals were detected in all the nuclei, colocalization was found only in the principal sensory trigeminal nucleus (Vp). About 64% of glutamatergic Vp neurons coexpressed VGLUT1 and VGLUT2, and the others expressed either VGLUT1 or VGLUT2, indicating that Vp neurons might be divided into three groups. We then injected retrograde tracer into the thalamic regions, including the posteromedial ventral nucleus (VPM) and posterior nuclei (Po), and observed that the majority of both VGLUT1- and VGLUT2-expressing Vp neurons were retrogradely labeled with the tracer. We further performed anterograde labeling of Vp neurons and observed immunoreactivies for anterograde tracer, VGLUT1, and VGLUT2 in the VPM and Po. Most anterogradely labeled axon terminals showed immunoreactivities for both VGLUT1 and VGLUT2 in the VPM and made asymmetric synapses with dendritic profiles of VPM neurons. On the other hand, in the Po, only a few axon terminals were labeled with anterograde tracer, and they were positive only for VGLUT2. The results indicated that Vp neurons expressing VGLUT1 and VGLUT2 project to the VPM, but not to the Po, although the functional differences of three distinct populations of Vp neurons, VGLUT1-, VGLUT2-, and VGLUT1/VGLUT2-expressing ones, remain unsettled.
|Selective p38α mitogen-activated protein kinase inhibitor attenuates lung inflammation and fibrosis in IL-13 transgenic mouse model of asthma. |
Ma, JY; Medicherla, S; Kerr, I; Mangadu, R; Protter, AA; Higgins, LS
Journal of asthma and allergy 1 31-44 2008
p38 Mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. We investigated the anti-inflammatory effects of a p38α-selective MAPK inhibitor (SD-282) in a mouse transgenic (CC10:IL-13) asthma model. The CC-10-driven over-expression of IL-13 in the mouse lung/airway has been shown to result in a remarkable phenotype recatitulating many features of asthma and characterized by eosinophilic and mononuclear inflammation, with airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystal, and airway sub-epitheilial fibrosis. Here we show how activated p38 MAPK can be observed in the lungs at the onset of asthma ie, around 8 weeks of age in both female and male mice. We also show that administration of a p38α MAPK selective inhibitor, SD-282 at 30 or 90 mg/kg, twice a day for a period of four weeks beginning at the onset of asthma, significantly reduced the inflammation (p less than 0.001); hyperplasia of airway epithelium (p less than 0.05); goblet cell metaplasia and mucus hypersecretion (p less than 0.001) and reduced lung remodeling and fibrosis (p less than 0.01), alleviating the severity of lung damage as measured by a composite score (p less than 0.05). Furthermore, SD-282 significantly reduced activated p38 MAPK in the lymphocytes and epithelial cells (p less than 0.001). Simultaneously, identical studies were conducted with an anti-fibrotic TGFβR1 kinase inhibitor (SD-208) which demonstrated anti-fibrotic but not anti-inflammatory properties. These findings suggest that the p38α-selective MAPK inhibitor may have dual therapeutic potential in attenuating both the inflammatory component and the fibrotic component of asthma and other Th2-polarized inflammatory lung diseases.Full Text Article
|Genetic deletion of Fatty Acid Amide Hydrolase results in improved long-term outcome in chronic autoimmune encephalitis. |
Michael Webb,Lin Luo,Jing Ying Ma,Chui-Se Tham
Neuroscience letters 439 2008
The enzyme Fatty Acid Amide Hydrolase (FAAH) is a key regulator of the endogenous levels of a family of biologically active lipid mediators, the fatty acid amides. These include anandamide, oleoyl ethanolamide and palmitoyl ethanolamide, and their effects are mediated by a variety of downstream targets including cannabinoid receptors and peroxisome proliferator-activated receptors (PPARs). Activation of both of these may have anti-inflammatory and neuroprotective effects. Levels of all three mediators are low in normal nervous tissue, but substantially elevated in mice lacking FAAH as a result of genetic deletion. There is a long anecdotal history of cannabis use by patients suffering from multiple sclerosis, and preclinical studies have indicated beneficial effects of cannabinoid receptor stimulation on both long-term outcome and acute muscle spasm in rodent models of multiple sclerosis (experimental autoimmune encephalitis; EAE). Thus far no report has appeared on the effect of inhibition of FAAH on the progression of EAE. Using a chronic mouse EAE model, we present data indicating that mice lacking FAAH experience an initial inflammatory phase of EAE similar in severity to wild type controls, but exhibited a more substantial clinical remission compared to wild type mice.
|Structure and implied functions of truncated B-cell receptor mRNAs in early embryo and adult mesenchymal stem cells: Cdelta replaces Cmu in mu heavy chain-deficient mice. |
Smadar Lapter, Idit Livnat, Alexander Faerman, Dov Zipori
Stem cells (Dayton, Ohio) 25 761-70 2007
Stem cells exhibit a promiscuous gene expression pattern. We show herein that the early embryo and adult MSCs express B-cell receptor component mRNAs. To examine possible bearings of these genes on the expressing cells, we studied immunoglobulin mu chain-deficient mice. Pregnant mu chain-deficient females were found to produce a higher percentage of defective morulae compared with control females. Structure analysis indicated that the mu mRNA species found in embryos and in mesenchyme consist of the constant region of the mu heavy chain that encodes a recombinant 50-kDa protein. In situ hybridization localized the constant mu gene expression to loose mesenchymal tissues within the day-12.5 embryo proper and the yolk sac. In early embryo and in adult mesenchyme from mu-deficient mice, delta replaced mu chain, implying a possible requirement of these alternative molecules for embryo development and mesenchymal functions. Indeed, overexpression of the mesenchymal-truncated mu heavy chain in 293T cells resulted in specific subcellular localization and in G(1) growth arrest. The lack of such occurrence following overexpression of a complete, rearranged form of mu chain suggests that the mesenchymal version of this mRNA may possess unique functions.
|Doublecortin-positive newly born granule cells of hippocampus have abnormal apical dendritic morphology in the pilocarpine model of temporal lobe epilepsy. |
Gabriel Maisonnave Arisi,Norberto Garcia-Cairasco
Brain research 1165 2007
Here, we describe dentate gyrus newly born granule cells morphology in rats' temporal lobe epilepsy pilocarpine model. Digital reconstruction of doublecortin-positive neurons revealed that apical dendrites had the same total length and number of nodes in epileptic and control animals. Nonetheless, concentric spheres analyses revealed that apical dendrites spatial distribution was radically altered in epileptic animals. The apical dendrites had more bifurcations inside the granular cell layer and more terminations in the inner molecular layer of epileptic dentate gyrus. Branch order analyses showed that second- and third-order dendrites were shorter in epileptic animals. Apical dendrites were concentrated in regions like the inner molecular layer where granular neuron axons, named mossy fibers, sprout in epileptic animals. The combination of altered dendritic morphology and number enhancement of the new granular neurons suggests a deleterious role of hippocampal neurogenesis in epileptogenesis. Being more numerous and with dendrites concentrated in regions where aberrant axon terminals sprout, the new granular neurons could contribute to the slow epileptogenesis at hippocampal circuits commonly observed in temporal lobe epilepsy.
|Preventive and therapeutic potential of p38 alpha-selective mitogen-activated protein kinase inhibitor in nonobese diabetic mice with type 1 diabetes. |
Medicherla, S; Protter, AA; Ma, JY; Mangadu, R; Almirez, R; Koppelman, B; Kerr, I; Navas, TA; Movius, F; Reddy, M; Liu, YW; Luedtke, G; Perumattam, J; Mavunkel, B; Dugar, S; Schreiner, GF
The Journal of pharmacology and experimental therapeutics 318 99-107 2006
Mitogen-activated protein kinases (MAPKs) and heat shock proteins (HSPs) are ubiquitous proteins that function within T cells in both normal and stress-related pathophysiological states, including type 1 diabetes. The nonobese diabetic (NOD) mouse spontaneously develops T cell-mediated autoimmune pancreatic beta cell destruction that is similar to type 1 diabetes in humans. Because p38 MAPKs have been shown to modulate T cell function, we studied the effects of a p38alpha MAPK-selective inhibitor, indole-5-carboxamide (SD-169), on the development and progression of type 1 diabetes in the NOD mouse. In preventive treatment studies, SD-169 significantly reduced p38 and HSP60 expression in T cells of the pancreatic beta islets. Following treatment, the incidence of diabetes as determined by blood glucose levels was significantly lower, and immuno-histochemistry of pancreatic beta islet tissue demonstrated significant reduction in CD5+ T cell infiltration in the SD-169 treatment group as compared with untreated NOD mice. In therapeutic studies using mildly and moderately hyperglycemic NOD mice, SD-169 treatment lowered blood glucose and improved glucose homeostasis. Furthermore, following cessation of SD-169 treatment, NOD mice showed significant arrest of diabetes. In conclusion, we report that this p38alpha-selective inhibitor prevents the development and progression of diabetes in NOD mice by inhibiting T cell infiltration and activation, thereby preserving beta cell mass via inhibition of the p38 MAPK signaling pathway. These results have bearing on current prophylactic and therapeutic protocols using p38alpha-selective inhibitors in the prediabetic period for children at high risk of type 1 diabetes, in the honeymoon period, and for adults with latent autoimmune diabetes.
|Expression of vesicular glutamate transporter 1 immunoreactivity in peripheral and central endings of trigeminal mesencephalic nucleus neurons in the rat. |
You Wang Pang, Jin-Lian Li, Kouich Nakamura, Shengxi Wu, Takeshi Kaneko, Noboru Mizuno
The Journal of comparative neurology 498 129-41 2006
The major neuronal components of the trigeminal mesencephalic nucleus (Vmes) are primary afferent neurons that convey proprioceptive information from the cranioorofacial regions. In the present study, we examined expression of vesicular glutamate transporters (VGLUTs), VGLUT1 and VGLUT2, in the primary afferent neurons of the Vmes (Vmes neurons) in neonatal and adult rats. VGLUT1 immunoreactivity was detected in the cell bodies of Vmes neurons in neonatal rats younger than 11 days old, but not in older rats. However, in situ hybridization signals for VGLUT1 mRNA were detected in both neonatal and adult rats. No VGLUT2 immunoreactivity was detected in Vmes neurons of neonatal or adult rats. VGLUT1 immunoreactivity was also seen in the peripheral sensory endings on the equatorial regions of intrafusal fibers of muscle spindles in the masseter muscles in both neonatal and adult rats. In adult rats injected with cholera toxin B subunit (CTb) into the masseter nerve, central axon terminals of Vmes neurons were identified on masseter motoneurons within the trigeminal motor nucleus (Vm) by transganglionically and retrogradely transported CTb. VGLUT1-immunopositive axon terminals in close apposition to CTb-labeled Vm motoneurons were also detected by dual-immunofluorescence histochemistry for VGLUT1/CTb. Electron microscopy after dual immunolabeling for VGLUT1/CTb by the VGLUT1/immunoperoxidase and CTb/immunogold-silver methods further revealed synaptic contact of VGLUT1- and CTb-immunopositive axon terminals upon CTb-labeled neuronal profiles within the Vm. These data indicate that VGLUT1 is expressed in both the central axon terminals and the peripheral sensory endings of Vmes neurons, although no VGLUT1 immunoreactivity was detectable in the cell bodies of Vmes neurons in adult rats.
|DONKEY ANTI-GOAT IgG AFFINITY PURIFIED, BIOTIN CONJUGATED ABSORBED FOR DUAL LABELING SECONDARY ANTIBODY|