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[ ABSTRACT] AIM:To investigate the effects of sulindac on oxidative stress in autism.METHODS:With an au-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of canonical Wnt pathway in the prefrontal cortex ( PFC) and hippocampus ( HC) of autistic rats treated with sulindac.The protein expression levels of glycogen synthase kinase 3β(GSK-3β), β-catenin and 4-hydroxynonenal (4-HNE) were ob-served by Western blotting.The mRNA expression of thioredoxin(Trx)1 and Trx2 was assessed by semi-quantitative RT-PCR.RESULTS:The protein level of GSK-3βand mRNA levels of Trx1 and Trx2 were lower, whereas the protein expres-sion levels ofβ-catenin and 4-HNE were higher in VPA group than those in control group.In contrast, the protein levels of GSK-3βwere significantly higher in the animals treated with both VPA and sulindac than those in VPA group, while the lev-els ofβ-catenin and 4-HNE were decreased.CONCLUSION:Sulindac attenuates oxidative stress in the pathogenesis of au-tism, suggesting the up-regulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and further facili-tates susceptibility to autism.
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[ABSTRACT]AIM:ToinvestigatetherolesofthecanonicalWntpathwayinautism.METHODS:Usinganau-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of the canonical Wnt pathway in the prefrontal cortex (PFC) and hippocampus formation (HF) of autistic rats.The expres-sion levels of glycogen synthase kinase 3β( GSK-3β) , phosphorylated GSK-3β, β-catenin and phosphorylated β-catenin were observed by Western blotting .The mRNA expression of GSK-3β, β-catenin, c-Myc and cyclin D1 was assessed by semi-quantitative RT-PCR.RESULTS:The results of Western blotting showed that inactivated GSK-3β(Ser9) phospho-rylation was significantly increased , and inhibitory β-catenin ( Ser33/37/Thr41 ) phosphorylation was obviously decreased compared with control group .The results of RT-PCR showed that the mRNA levels of β-catenin, c-Myc and cyclin D1 in-creased, and GSK-3βwas significantly enhanced in VPA-exposed rats compared with the controls .CONCLUSION: In-creased activity of canonical Wnt pathway in the PFC and HF of autistic rats may contribute to the susceptibility to autism .
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BACKGROUND: Studies have confirmed that Atorvastatin drugs can increase the number of endothelial progenitor cells significantly in vitro, as well as the content of vascular endothelial growth factor(VEGF). OBJECTIVE: To investigate the effect of Atorvastatin on VEGF expression in necrotic femoral heads of rabbits. DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed at the Department of Orthopedic Surgery, Renmin Hospital of Wuhan University, from September 2007 to November 2008. MATERIALS: Forty-five male and female healthy New Zealand white rabbits weighing 2.5-3.5 kg were randomly divided into normal control group, model control group and AtorvastaUn group, 15 rabbits in each group. METHODS: Nitrogen refrigeration was used to develop femoral head necrosis models of rabbits in the model control and Atorvastatin groups. Two weeks after modeling, the animals in the Atorvastatin group were administered intragastically with Atorvastatin, normal control and model control group were treated with the same volume of normal saline. MAIN OUTCOME MEASURES: Each five rabbits were sacrificed at the 4th, 8th, and 12th weeks respectively for general observation, X-ray and histological observation. VEGF protein expression was assessed by immunohistochemistry method and VEGF mRNA level was assessed by reverse transcription - polymerase chain reaction method. RESULTS: The VEGF protein and mRNA levels in the model control and Atorvastatin groups were obviously lower than those in the normal control group, while the VEGF protein and mRNA levels in the Atorvastatin group were much higher than those in the model control group at the 8th and 12th weeks alter the treatment with Atorvastatin (P < 0.05). CONCLUSION: Atorvastatin can significantly upregulate the expression of VEGF, which is probably an effective clinical treatment to avascular necrosis of the femoral head.
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It has been known that the Alzheimer's disease(AD)is related closely with a synaptic failure,and the p21-activated kinase(PAK)is well documented to play an important role in the regulation of the synaptie functions.However,the relationship between thePAK and the pathology of AD is unclear.In the present study,we examined the expressions of the PAK3(one subtype ofPAK),phospho-rylated-PAK(pPAK) and β-amyloid42(Aβ42,β-amyloid with 42 peptides)in an APP/PS1 double transgenie mouse model of AD andthe morphologies of geurOtlS in the hippocampus at different ages.The Western Blot results showed that the expression of PAK remainedunchanged,while,the expression of pPAK decreased largely at the age of 32 weeks and further decreased significantly with aging in thehippocampus of the APP/PS1 transgenic mouse.A1342 levels in the hippocampus were detected to increase as early as the age of 22 weeks,and kept the increase to continue with aging.The morphological results showed no obvious neuron loss in the sections of Nissl staining,while serious distonion and disorder of the dendrites of the hippocampal neurons were observed on the sections of Gelgi staining in theAPP/PS1 transgenic mouse.The present results suggested that it seemed something wrong in the processes of phospholization of PAK,butnot in the expression of the PAK itself;the toxic Aβ42 might affect the PAK in its phospholization,which in turn directly influence thedendritic development in the hippocampal neurons and cause the dendrites distorting and disordering.
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It has been reported that the small type of neurons in the dorsal root ganglion (DRG) play an important role in pain regulation by a presynaptic mechanism via the metabotropic type-B γ-aminobutyric acid receptors ( GABABR ). In order to understand whether the 2populations of the small type of the neurons, peptidergic and nonpeptidergic, in DRG share the same role, immunoflourescent histochemical methods and confocal laser scanning microscope were employed to investigate the expression of the GABABR in the peptidergic and nonpeptidergic small DRG neurons. The results revealed that 92% of the peptidergic and 90% of nonpeptidergic small DRG neurons express GABABR in their perikarya and central processes, which distribute in the various laminae of the spinal dorsal horn. These results suggest both the peptidergic and nonpeptidergic populations of the small neurons in the DRG share similar role in pain modulation via presynaptic mechanisms but in given laminae of the spinal dorsal horn.
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Amygdala (AM) plays crucial roles in emotional learning, memory and behavior. These functions of AM are carried out by three main subnuclei (lateral nucleus, basolateral nucleus and central nucleus) in AM and closely related with a transcription factor, cAMP- responsive element binding protein (CREB) in the neurons of the AM. CREB can be phosphorylated (pCREB) in many kinds of neuronal processes to regulate the synthesis of proteins for the formation of memory processes. In order to identify what neuronal types express pCREB and how the pCREB levels changed at different time intervals after an emotional stress stimulation, the present study is designed to investigate pCREB-, glutamate (Glu)- and parvalbumin (PV)- immunoreactive (IR) profiles in AM and the levels of pCREB in AM after a stress of forced swimming (FS). The results showed that the pCREB expressed in the Glu-IR neurons but not in the PV-IR neurons, and the expression level of the pCREB increased dramatically after the stress. The present results suggested that pCREB modulates the emotional processes through the Glu-IR neurons and that the pCREB greatly upregulated to response to the emotional stimuli.
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As the elements of local neuronal circuits, parvalbumin (PV)-containing interneurons in the basolateral nucleus (BL) of the amygdala play an important role in the amygdaloid functions of emotion, learning and memory. In order to investigate how the PV-containing interneurons in the BL are controlled, the synapses established on PV- containing interneurons in the BL of the rat amygdala were examined under immunoelectron microscopy using the double labeling methods with anti-PV and anti-dopamine (DA) antibodies for a reference of dopaminergic axon terminals. The results show that the PV immunoreactive (IR) neurons formed the synapses mainly on the dendritic structures from shafts of the dendrites to median and small dendritic branches. 68% of the synapses on the PV-IR profiles were formed by unlabeled axon terminals, and 32 % of them were formed by DA- (21 % ) and PV- (11 % )IR axon terminals. Majority of the synapses on the PV-IR neurons formed by unlabeled axon terminals were symmetric type, and only a small a mount of them were asymmetric that were observed between the PV-IR spines and unlabeled axon terminals and in the serial synapses in which an unlabeled axon terminal symmetrically contacted to another unlabeled axon terminal that, in turn, synapsed asymmetrically to the PV-IR dendritic profiles. The synapses formed between the PV-IR profiles and DA- or PV-IR axon terminals were exclusively symmetric. The present results suggest that the PV-containing interneurons in the BL of the rat amygdala were controlled by an inhibitory network formed by the symmetric synapses around them, among which the DA system was included.
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Fifty adult lower limbs were studied macromicroscopically to reveal the extrinsic blood vessels of the menisci of the knee joint. It was found that the menisci were supplied from 2 sources, the genicular branches (except the superior lateral genicular branch) of the popliteal artery, and the descending branch of the descending genicular artery. A pair of additional genicular branches with independent stems from the popliteal artery, named as the posterior medial and the posterior lateral genicular arteries by the authors, constantly supplied the posterior part of both the menisci. The arterial branches formed a circular anastomotic arch around the menisci with small branches springing from the arch and getting into the menisci. The arterial arch communicated with the femoral and the popliteal arteries and became an important stem of a reentry channol in cases of popliteal artery occlusion.
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Objective To understand the base of the neuroanatomy underlying the nociceptive syndrome occurring in cervical zygapophyseal joints,in which pain in upper limb was accompanied. Methods The capsules of the C4-T1 zygapophyseal joints of SD rats were immunostained with anti-calcitonin-gene-related peptide(CGRP) antibody,and a modified tricetry labeling was done as following:the fluorescents,fast blue(FB) and nucleus yellow(NY),were injected,respectively,into the right radial nerve and capsules of the zygapophyseal joints of neck,then, the ipsilateral dorsal root ganglia(DRG) were sectioned and the retrogradely labeled sensory neurons in the DRG were observed and photographed,finally,the sections were further immunostained with anti-CGRP antibody,eventually,the neurons in both of the photos labeled by fluorescents and anti-CGRP antibody were comparatively observed and analyzed. Results The nervers fibers containing CGRP distributed throughout the capsules of the zygapophyseal joints from C4-T1 in the rat.Most of these fibers coursed straightly and individually,and some of them anastomosed to each other to form the networks of the nerve fibers.The neurons retrograde labeled by fluorescents were observed in each of the DRG from C5-T1.These neurons shared a labeling populations of FB single(76%),NY single(16%) and FB/YN double labeling(8%) respectively.Moreover, about 40% fluorescents labeled neurons were immunoreacted to CGRP.Conclusion The peripheral processes from a population of sensory neurons that contain CGRP in the cervical DRG simultaneously innervated both the capsules of cervical zygapophyseal joints and the fore limb with the radial nerve.The present results suggest that the nociceptive syndrome of cervical zygapophyseal joints with pain in human upper limb might be the referred pain occurring in the level of the DRG.
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In order to study the arteries of menisci, both inside and outside themselves, a series of specimens were used and prepared by macro-micro-anatomical, histological, translucent and SEM methods. The arteries of the posterior part of menisci come from the posterior medial and lateral genicular arteries. Those of their anterior part come from the inferior lateral genieular artery, superior and inferior medial genicular arteries, or descending genicular artery, and may be divided into three types according to their sources. The meniscal branches of these arteries anastomose with each other to form a perimeniscal arterial circle which is continuous at its anterior part and interrupted beneath the tibial collateral ligament and popliteal tendon to form an avascular area. The arterial circle is important for collateral circulation around the knee and also provides an anatomical basis for the selection of appraoches in meniscal operation. The nourishing arteriolae, arising from the arterial circle from an arteriolar network around the menisci and give off arteriolae into the body and horn of the menisci. Healing process of the injured meniscus is intimately related with the vascular architecture inside it and recover more easily in the horn and peripheral part of the body due to rich microvasculature in these parts.