Immunohistochemical analysis of tau phosphorylation and astroglial activation with enhanced leptin receptor expression in diet-induced obesity mouse hippocampus

AbstractAccumulating evidence indicates that obesity is an independent risk factor for developing Alzheimer disease (AD). Recent studies have shown that diet-induced obesity (DIO) enhances AD-related pathologies in transgenic mouse models of the disease. DIO increases amyloid β (Aβ) deposition in amyloidogenic transgenic mice and enhances tau phosphorylation in tau transgenic mice. However, it remains unclear whether DIO also enhances AD-related pathological processes in wild-type (WT) mice. In this study, we examined the effects of DIO on Aβ and tau pathology in WT mice using immunohistochemistry. In addition, we evaluated the protective effect of voluntary exercise on the DIO-induced pathological changes. DIO caused tau phosphorylation and astroglial activation in the hippocampus in WT mice. Interestingly, these changes were associated with enhanced astrocytic leptin receptor (LepR) expression and mild microgliosis, but not Aβ accumulation. Although phosphorylated tau staining was only observed in the hippocampus, astrogliosis and microgliosis were present in both the amygdala and hippocampus. However, no apparent neuronal loss was observed. Voluntary exercise prevented these DIO-induced pathological changes. Our results demonstrate for the first time that DIO causes tau phosphorylation and that astrocytic LepR might be involved in the pathological process in WT mouse hippocampus. Our findings also suggest that physical exercise is a promising strategy for the prevention of AD in patients with obesity

Diagnosis and treatment of NMO spectrum disorder and MOG-encephalomyelitis

Neuromyelitis optica spectrum disorders (NMOSD) are autoantibody mediated chronic inflammatory diseases. Serum antibodies (Abs) against the aquaporin-4 water channel lead to recurrent attacks of optic neuritis, myelitis and/or brainstem syndromes. In some patients with symptoms of NMOSD, no AQP4-Abs but Abs against myelin-oligodendrocyte-glycoprotein (MOG) are detectable. These clinical syndromes are now frequently referred to as "MOG-encephalomyelitis" (MOG-EM). Here we give an overview on current recommendations concerning diagnosis of NMOSD and MOG-EM. These include antibody and further laboratory testing, MR imaging and optical coherence tomography. We discuss therapeutic options of acute attacks as well as longterm immunosuppressive treatment, including azathioprine, rituximab, and immunoglobulins

Relapse of Neuromyelitis Optica Spectrum Disorder Associated with Intravenous Lidocaine

Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients; however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out

Study on the Teaching Strategy of an Elementary School and Improving the Program for Training Students to be Teachers of University (1) : In the Case of Japanese Language, Arithmetic and Science

　本研究は，教科内容構成の考え方に基づいて小学校の授業づくりのあり方を検討するとともに，それをふまえることで大学の教員養成プログラムの授業が具体的にどのように改善されるかを明らかにしようとしたものである。教科内容構成とは，教員養成において従来から課題とされてきた教科の内容に関わる知識・技能と教科の指導法に関わる知識・技能の分離という問題を克服するために提案されたものである。教科内容構成は，教科の内容と指導法に関わる知識・技能を統合し，それらを応用して，教師が自ら「どのような内容をどのように教えるべきか」を考え，授業づくりに取り組むことができるようになるための考え方を示すものであり，本研究では教員養成プログラムにおける具体的な授業プランを提示してそれを明らかにしていく。本稿では，特に，小学校の国語科，算数科，理科を事例として論じていくことにしたい

Reverse loading tests of steel tube under biaxial stress states

Biaxial loading and reverse loading tests were performed using seamless carbon steel tubes. Biaxial stress components in the axial and circumferential directions were applied to the tubular specimens using a servo-controlled multiaxial tube expansion testing machine developed by Kuwabara and Sugawara (2013). The tubular specimens were loaded under linear tensile stress paths. Contours of plastic work were measured in the principal stress space, and the differential hardening (DH) behavior was observed; the shapes of the contours of plastic work changed with an increase in plastic work. In addition, small uniaxial tensile specimens were fabricated from the mother tube wall in axial and hoop directions, and tension–compression reverse loading tests were performed to quantitatively evaluate the Bauschinger effect of the test material. Moreover, bilinear stress path experiments were performed to investigate the effects of axial prestraining on the change in the Bauschinger effect; compressive preloading in the axial direction (first loading) was followed by the application of linear stress paths in the first quadrant of the principal stress space (second loading). The measured Bauschinger effect in the second loading was different from those measured in the uniaxial reverse loading tests for the as-received material. The material model will be utilized to improve the accuracy in the numerical analyses of the cold working processes for fabricating steel tubes

Study on the Teaching Strategy of an Junior High School and Improving the Program for Training Students to be teachers of University (1) : In the Case of Japanese Language, Arithmetic, Science and Social Studies

　本研究は，教科内容構成の考え方に基づいて中学校の授業づくりのあり方を検討するとともに，それをふまえることで大学の教員養成プログラムの授業が具体的にどのように改善されるかを明らかにしようとしたものである。教科内容構成とは，教員養成において従来から課題とされてきた教科の内容に関わる知識・技能と教科の指導法に関わる知識・技能の分離という問題を克服するために提案されたものである。教科内容構成は，教科の内容と指導法に関わる知識・技能を統合し，それらを応用して，教師が自ら「どのような内容をどのように教えるべきか」を考え，授業づくりに取り組むことができるようになるための考え方を示すものであり，本研究では教員養成プログラムにおける具体的な授業プランを提示してそれを明らかにしていく。本稿では，特に，中学校の国語科，数学科，理科，社会科を事例として論じていくことにしたい

Sensitization to secretoglobin and lipocalins in a group of young children with risk of developing respiratory allergy

Background: Multiple sensitizations in early age have been reported to be a risk for development of asthma. This study evaluates the emergence and evolution of IgE to aeroallergens among a cohort of children with physician-diagnosed atopic dermatitis and/or showing food allergy symptoms and to examine the relation to asthma development. Methods: Three-hundred and four children (median age 13.4 months at entry) with food allergy symptoms and/or atopic dermatitis without asthma at inclusion were analysed for IgE antibodies against food-, indoor- and outdoor-allergens and pet allergen components and correlated to the individuals’ outcome on asthma inception. Results: At 2 years of follow-up, physician-diagnosed asthma was 19.7% (n = 49) and asthma diagnosed any time was 24% (n = 67). History of persistent cough and asthma of father, combination of milk- and wheat-allergy symptoms and dual sensitization to house dust mite and Japanese cedar were independent risk factors for asthma. Sensitization to dog was the most prevalent inhalant allergen at entry. Asthma children had a higher proportion of sensitization to dog, cat and horse allergens at entry compared with non-asthma children. Being sensitized to both food, house dust mite and pet allergens was strongly associated with asthma (p = 0.0006). Component resolved diagnosis for dog and cat allergens showed that IgE antibodies to Can f 1 and Fel d 1 was common even at very young age. Conclusions: Early sensitization to inhalant allergens increases the risk of developing asthma as well as having milk and wheat allergy symptoms. Sensitization to dog, was common at an early age despite dog ownership. Sensitization to secretoglobin and lipocalins and less to serum albumins explained the pet sensitization

Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival.

This is the published version. Copyright 1994 The Rockefeller University Press.To elucidate mechanisms underlying neuroprotective properties of astrocytes in brain ischemia, production of neurotrophic mediators was studied in astrocytes exposed to hypoxia/reoxygenation (H/R). Rat astrocytes subjected to H/R released increased amounts of interleukin (IL) 6 in a time-dependent manner, whereas levels of tumor necrosis factor and IL-1 remained undetectable. IL-6 transcripts were induced in hypoxia and the early phase of reoxygenation, whereas synthesis and release of IL-6 antigen/activity occurred during reoxygenation. Elevated levels of IL-6 mRNA were due, at least in part, to increased transcription, as shown by nuclear runoff analysis. The mechanism stimulating synthesis and release of IL-6 antigen by astrocytes was probably production of reactive oxygen intermediates (ROIs), which occurred within 15-20 minutes after placing hypoxia cultures back into normoxia, as the inhibitor diphenyl iodonium inhibited the burst of ROIs and subsequent IL-6 generation (blockade of nitric oxide formation had no effect on ROI generation or IL-6 production). Enhanced IL-6 generation was also observed in human astrocytoma cultures exposed to H/R. Survival of differentiated PC12 cells exposed to H/R was potentiated by conditioned medium from H/R astrocytes, an effect blocked by neutralizing anti-IL-6 antibody. In a gerbil model of brain ischemia, IL-6 activity was lower in the hippocampus, an area sensitive to ischemia, compared with IL-6 activity in the cortex, an area more resistant to ischemia. IL-6 antigen, demonstrated immunohistochemically, was increased in astrocytes from ischemic regions of gerbil brain. These data suggest that H/R enhances transcription of IL-6, resulting in increased translation and release of IL-6 antigen after the burst of ROI generated early during reoxygenation. Release of IL-6 from astrocytes could exert a paracrine neurotrophic effect in brain ischemia

Diagnosis and Treatment of NMO Spectrum Disorder and MOG-Encephalomyelitis

Neuromyelitis optica spectrum disorders (NMOSD) are autoantibody mediated chronic inflammatory diseases. Serum antibodies (Abs) against the aquaporin-4 water channel lead to recurrent attacks of optic neuritis, myelitis and/or brainstem syndromes. In some patients with symptoms of NMOSD, no AQP4-Abs but Abs against myelin-oligodendrocyte-glycoprotein (MOG) are detectable. These clinical syndromes are now frequently referred to as “MOG-encephalomyelitis” (MOG-EM). Here we give an overview on current recommendations concerning diagnosis of NMOSD and MOG-EM. These include antibody and further laboratory testing, MR imaging and optical coherence tomography. We discuss therapeutic options of acute attacks as well as longterm immunosuppressive treatment, including azathioprine, rituximab, and immunoglobulins