Genes Related to Oxytocin and Arginine-Vasopressin Pathways: Associations with Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication deficits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood, several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin (OXT) and arginine-vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a (AVPR1a), OXT receptor (OXTR), the oxytocinase/vasopressinase (LNPEP), and ADP-ribosyl cyclase (CD38).     

NMDA受体拮抗剂MK—801阻断福尔马林诱导的大鼠脊髓c—Fos表达

大量证据表明，兴奋性氨基酸（ｅｘｃｉｔａｔｏｒｙａｍｉｎｏａｃｉｄｓ，ＥＡＡｓ）是脊椎动物中枢神经系统的兴奋神经递质，并参与伤害性信息的一级传递，但对ＮＭＤＡ受体在不同伤害性信息传递中的作用却颇有争议，本实验采用免疫组化方法显示脊髓Ｆｏｓ样免疫活性（Ｆｏｓ－ｌｉｋｅｉｍｍｕｎｏｒｅａｃｔｉｖｉｉｔｙ，ＥＬＩ）神经元，观察化学性伤害性刺激物福尔马林（５％，１５０μｌ）足底注射对脊髓ｃ－Ｆｏｓ表达的诱     

大鼠脊髓不同类型阿片受体在介导下丘脑弓状核刺激镇痛中的作用

在轻度麻醉大鼠,电刺激下丘脑弓状核(ARH)大大延长了辐射热甩尾潜伏期,脊髓蛛网膜下腔注射(ith)κ阿片受体阻断剂nor-BNI对大鼠基础痛阈及ARH刺激引起的镇痛效应无明显影响,ithδ阿片受体阻断剂ICI 174864和不可逆的“阿片受体阻断剂β-FNA对基础痛阈仍无影响,但剂量依赖性地减弱了ARH刺激镇痛。结果提示,脊髓内的δ和μ受体参与了ARH对脊髓伤害性反射的下行性抑制。     

Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat

1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ)–the endogenous ligand for the orphan opioid receptor (called, e.g., ORL₁ and LC132)–on pain modulation in the rat. We used the tail-flick assay as a nociceptive index.
2. When injected into a cerebral ventricle, OFQ (4 fmol–10 nmol) has no effect on basal tail-flick latency by itself at any dose, but dose-dependently antagonizes systemic morphine analgesia (400 fmol–50 nmol).
3. Injected intrathecally, OFQ (3 and 10 nmol) displayed an analgesic effect without producing motor dysfunction, and potentiated morphine analgesia (1 and 10 nmol).
4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL₁ receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms. However, no such precipitation was observed by OFQ in morphine-dependent rats.

     

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.     

Clinical characteristics and therapeutic strategies of atypical meningioma

Background  Atypical meningioma accounts for about 4.7% to 7.2% of all kinds of meningiomas, which is invasive with a relatively high recurrence and mortality. The objective of this study was to investigate the clinical manifestations and therapeutic strategies of atypical meningioma.

Methods  A total of 74 patients who underwent surgical treatment and pathologically confirmed for atypical meningioma in Neurosurgery Department of Beijing Tiantan Hospital from January 2003 to December 2008 were enrolled in this study. The characteristics of the tumors as well as therapeutic regimens and follow-up data were reviewed. After surgery, 56 patients underwent radiotherapy. Patients were followed up for about 3.5 years (range, 0.5–6.0 years), and 58 patients completed follow-up.

Results  Of the 58 patients who completed follow-up, good recovery was found in 30, neurological dysfunction in 15, and death in 13. Of the 58 patients, 21 had recurrent meningioma and 18 underwent a second surgery.

Conclusions  Atypical meningioma is difficult to manage, with a high recurrence rate and poor survival. The extent of tumor resection and histological grade are the key determinants of outcome. Radiation therapy can be used as an adjunctive treatment after total or partial resection.

     

Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain

Our previous study has reported that electroacupuncture (EA) at low frequency of 2 Hz had greater and more prolonged analgesic effects on mechanical allodynia and thermal hyperalgesia than that EA at high frequency of 100 Hz in rats with neuropathic pain. However, how EA at different frequencies produces distinct analgesic effects on neuropathic pain is unclear. Neuronal plastic changes in spinal cord might contribute to the development and maintenance of neuropathic pain. In the present study, we investigated changes of spinal synaptic plasticity in the development of neuropathic pain and its modulation by EA in rats with neuropathic pain. Field potentials of spinal dorsal horn neurons were recorded extracellularly in sham-operated rats and in rats with spinal nerve ligation (SNL). We found for the first time that the threshold for inducing long-term potentiation (LTP) of C-fiber-evoked potentials in dorsal horn was significantly lower in SNL rats than that in sham-operated rats. The threshold for evoking the C-fiber-evoked field potentials was also significantly lower, and the amplitude of the field potentials was higher in SNL rats as compared with those in the control rats. EA at low frequency of 2 Hz applied on acupoints ST 36 and SP 6, which was effective in treatment of neuropathic pain, induced long-term depression (LTD) of the C-fiber-evoked potentials in SNL rats. This effect could be blocked by N-methyl-d-aspartic acid (NMDA) receptor antagonist MK-801 and by opioid receptor antagonist naloxone. In contrast, EA at high frequency of 100 Hz, which was not effective in treatment of neuropathic pain, induced LTP in SNL rats but LTD in sham-operated rats. Unlike the 2 Hz EA-induced LTD in SNL rats, the 100 Hz EA-induced LTD in sham-operated rats was dependent on the endogenous GABAergic and serotonergic inhibitory system. Results from our present study suggest that (1) hyperexcitability in the spinal nociceptive synaptic transmission may occur after nerve injury, which may contribute to the development of neuropathic pain; (2) EA at low or high frequency has a different effect on modulating spinal synaptic plasticities in rats with neuropathic pain. The different modulation on spinal LTD or LTP by low- or high-frequency EA may be a potential mechanism of different analgesic effects of EA on neuropathic pain. LTD of synaptic strength in the spinal dorsal horn in SNL rats may contribute to the long-lasting analgesic effects of EA at 2 Hz.     

Case-control association study of Disrupted-in-Schizophrenia-1 (DISC1) gene and schizophrenia in the Chinese population

Disrupted-in-Schizophrenia-1 (DISC1) has first been identified as a candidate gene for schizophrenia through study of a Scottish family with a balanced (1; 11) (q42.1; q14.3) translocation. Lots of linkage and association studies supported DISC1 as a risk factor for schizophrenia. In this study, we genotyped three SNPs in DISC1 using a set of Han Chinese samples of 560 schizophrenics and 576 controls. No positive association was detected in the whole samples but analysis of allele frequencies in female samples showed weak association between SNP rs2295959 and the disease (chi(2)=6.188, P=0.0135, OR=0.728, 95% CI=0.567-0.935). Our results provide further evidence for sex difference for the effect of the gene on the aetiology of schizophrenia. Our findings also would encourage further studies, particularly family-based association studies with larger samples, to analyze the association between DISC1 and schizophrenia.     

Electroacupuncture frequency-related transcriptional response in rat arcuate nucleus revealed region-distinctive changes in response to low- and high-frequency electroacupuncture

Electroacupuncture (EA) has been clinically applied for treating different medical conditions, such as pain, strain, and immune diseases. Low- and high-frequency EAs have distinct therapeutic effects in clinical practice and experimental studies. However, the molecular mechanism of this difference remains obscure. The arcuate nucleus (Arc) is a critical region of the hypothalamus and is responsible for the effect of EA stimulation to remote acupoints. Gene expression profiling provides a powerful tool with which to explore the basis of physiopathological responses to external stimulus. In this study, using cDNA microarray, we investigated gene expressions in the rat Arc region induced by low-frequency (2-Hz) and high-frequency (100-Hz) EAs to two remote acupoints, zusanli (ST36) and sanyinjiao (SP6). We have found that more genes were differentially regulated by 2-Hz EA than 100-Hz EA (154 vs. 66 regulated genes/ESTs) in Arc, especially those related to neurogenesis, which was confirmed by qRT-PCR. These results demonstrate that the expression level of genes in the Arc region could be effectively regulated by low-frequency EA, compared with high-frequency EA, helping to uncover the mechanisms of the therapeutic effects of the low-frequency EA. Our results also indicate different-frequency EAs are spatially specific.