Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats

<p>Abstract</p> <p>Background</p> <p>The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes and is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain. However, the lack of available specific inhibitors and/or activators for GLT-1 makes it difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic pain. In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats.</p> <p>Results</p> <p>Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2–21 days after the infusion. Transgene expression was primarily localized to astrocytes. The spinal GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive responses in naive rats, whereas it significantly reduced the inflammatory mechanical hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were infused 7 or 14 days after the nerve ligation.</p> <p>Conclusion</p> <p>These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation. Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.</p

Identification of trehalose dimycolate (cord factor) in Mycobacterium leprae

AbstractGlycolipids of Mycobacterium leprae obtained from armadillo tissue nodules infected with the bacteria were analyzed. Mass spectrometric analysis of the glycolipids indicated the presence of trehalose 6,6′-dimycolate (TDM) together with trehalose 6-monomycolate (TMM) and phenolic glycolipid-I (PGL-I). The analysis showed that M. leprae-derived TDM and TMM possessed both α- and keto-mycolates centering at C78 in the former and at C81 or 83 in the latter subclasses, respectively. For the first time, MALDI-TOF mass analyses showed the presence of TDM in M. leprae

Brain correlates of phasic autonomic response to acupuncture stimulation: An event‐related fMRI study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100160/1/hbm22091.pd

Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology☆☆☆

Objective: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS. Methods: We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. Results: For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Conclusions: Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery

Serum amyloid A-induced IL-6 production by rheumatoid synoviocytes

AbstractIn this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-κB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-κB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis

Factor Structure of the Autism-Spectrum Quotient Japanese Version

The Autism-Spectrum Quotient is a self-report of autistic traits in adults with normal intelligence. Some studies have examined its factor structure. However, no research has tested how many factors the Japanese version of the measure has. Therefore, this study examined previous factor structure as well asthe scale’s reliability and validity in an undergraduate sample (N=309). Confirmatory factor analysis revealed 5 factors: Sociability, Social Cognition, Narrow Focus, Resistance to Change, and Interest in Patterns. The scale had adequate internal consistency and model fit. For these reasons, Japanese version of the Autism-Spectrum Quotient can be considered to have a 5-factor structure.　Autism-Spectrum Quotient （AQ）は，自閉スペクトラム症特性を測定する質問紙である。このAQ は社会的スキル，注意の切り替え，細部への注意，コミュニケーション，想像力という5つの下位尺度からなるとされているが（Baron-Cohen et al., 2001），これらの下位尺度は理論的に導かれたものであり，因子分析の結果抽出されたものではない。一方，Lau et al. （2013）が因子分析を行った結果，Baron-Cohen et al. （2001）において示されていた下位尺度とは部分的に異なる因子が得られた。そこで本研究では，Baron-Cohen et al. （2001）による原版の5因子構造と，Lau et al. （2013）の因子分析に基づく5因子構造のどちらが日本のデータにより適合しているのか検討を行った。その結果，Baron-Cohen et al. （2001）の原版に基づき作成された因子モデルよりも，Lau et al. （2013）の因子分析に基づいて作成された因子モデルの方が比較的適合度がよいことが明らかとなった

Investigation on the Autistic Spectrum Tendency of University Student : Using AQ－J－10

Students with autistic traits are particularly likely to be isolated because of interpersonal problems. Therefore, early detection of such traits and support for these students is necessary. This study investigates such traits with the Autism-Spectrum Quotient-Japanese version-10 (AQ-J-10) in a sample of 646 undergraduate students. Of the sample, 9.8％ exhibited high levels of autistic traits (AQ＞7). Analysis of relationship between university department and the prevalence of high autistic traits showed that high autistic traits were more prevalent in students from the science and engineering than other departments. This result suggests that university faculty in natural sciences departments should obtain in-depth awareness and understanding of autism.自閉スペクトラム症傾向の学生は，対人関係の問題により孤立化しやすい。そのため，彼らを早期に発見し，支援へと繋げることが必要である。646 名の大学生を対象に，自閉性スペクトル指数10 項目版 (AQ‒J‒10) を用いて調査を行った結果，カットオフポイントを超える学生の割合は9.8％であった。対象者の所属学部ごとに，カットオフポイントを上回る学生の割合を算出したところ，理工学系の学生において有意に高いことが示された。このため，特に自然科学系の学部では，支援を行う立場にある教職員が自閉スペクトラム症傾向の認識を深めることが重要である