Takayuki Sogabe

Effect of peripheral nerve injury on nuclear magnetic resonance relaxation times of rat skeletal muscle.

RATIONALE AND OBJECTIVES The authors evaluate the changes in magnetic resonance (MR) relaxation times of rat skeletal muscles in vivo after nerve injury and during neural recovery, and determine the major determinants of relaxation times. MATERIALS Magnetic resonance relaxation times, blood volume, and water and fat content were examined after nerve injury and during recovery with time course. RESULTS Nerve injury led to longer T2 values compared with controls, but there were no significant changes in T1 values. After the initial prolongation of T2 after nerve injury, no changes were observed. Neural recovery resulted in a return of T2 values to normal. The time course of changes in blood volume was similar to that of changes in T2, and T2 values were correlated strongly with 19-fluorine-MR spectroscopy estimates of blood volume (r2 = 0.94). CONCLUSIONS T2 values may be useful to monitor recovery after nerve injury and may be related to the blood volume in skeletal muscle.

Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice

Recent evidence supports the amyloid cascade hypothesis that a pathological change of amyloid β (Aβ) in the brain is an initiating event in Alzheimers disease (AD). Accordingly, modulating the abnormal Aβ aggregation is considered a potential therapeutic target in AD. Curcumin, a low-molecular-weight polyphenol derived from the well-known curry spice turmeric, has shown favorable effects on preventing or treating AD pathology. The present study investigated the effects of curcumin and 2 novel curcumin derivatives, FMeC1 and FMeC2, on AD pathology in APPswe/PS1dE9 double transgenic mice. Mice fed a chow diet that contained FMeC1 for 6 months showed a reduction in insoluble Aβ deposits and glial cell activity together with reduced cognitive deficits, compared to animals receiving a control diet or with curcumin or FMeC2 in their diet. Both curcumin and FMeC1 modulated the formation of Aβ aggregates; however, only FMeC1 significantly attenuated the cell toxicity of Aβ. These results indicate that FMeC1 may have potential for preventing AD.

On-site diagnosis of H. pylori infection by urine

We have recently developed an on-site diagnostic kit for H. pylori infection using urine (utilizing immunochromatographic method employing a nitrocellulose membrane coated by extracted H. pylori antigen). Accordingly, we investigated its usefulness in 155 consecutive dyspeptic patients using the 13C urea breath test as a gold standard and further compared its performance with two commercially available rapid diagnostic kits that use whole blood (Helisal Rapid Blood, and ImmunoCard H. pylori). As the results, the urine based on-site diagnostic kit provided 95.9% sensitivity and 87.9% specificity with 92.9% accuracy, which were comparable or even better than that of both rapid whole blood tests, suggesting its usefulness in screening of H. pylori infection.

EFFECTS OF VASODILATORS ON THE SIGNAL INTENSITY OF PERFLUOROCARBON MONITORED BY IN VIVO 19F-NMR SPECTROSCOPY

The effects of vasodilators on peripheral vessels were examined by monitoring the 19F-NMR signal of perfluorocarbon in vivo. Nitroglycerin, a venodilator that acts mainly on venous smooth muscle, increased the signal intensity of FC-43, whereas hydralazine, a typical arteriolar dilator that acts on arteriolar smooth muscle, decreased the signal intensity. These results indicate that the in vivo effects of vasodilators on smooth muscles of the venous and arterial systems are reflected by their effects on the signal intensity of FC-43.

Venodilatory effect of pranidipine, a calcium channel blocker, monitored with perfluorocarbon in vivo 19F-NMR spectroscopy

We previously reported that the (19)F-NMR signal intensity of perfluorocarbon was increased by a venodilator, nitroglycerine, and decreased by an arteriodilator, hydralazine. In the present study, we demonstrated that pranidipine, a calcium channel blocker, increased the intensity of the FC-43 signal, while nifedipine, a prototype of calcium channel blockers, did not. These results suggest that pranidipine dilates the venous system in contrast to nifedipine.

Fluorine-19 magnetic resonance imaging probe for the detection of tau pathology in female rTg4510 mice

Aggregation of tau into neurofibrillary tangles (NFTs) is characteristic of tauopathies, including Alzheimers disease. Recent advances in tau imaging have attracted much attention because of its potential contributions to early diagnosis and monitoring of disease progress. Fluorine‐19 magnetic resonance imaging (19F‐MRI) may be extremely useful for tau imaging once a high‐quality probe has been formulated. In this investigation, a novel fluorine‐19–labeling compound has been developed as a probe for tau imaging using 19F‐MRI. This compound is a buta‐1,3‐diene derivative with a polyethylene glycol side chain bearing a CF3 group and is known as Shiga‐X35. Female rTg4510 mice (a mouse model of tauopathy) and wild‐type mice were intravenously injected with Shiga‐X35, and magnetic resonance imaging of each mouses head was conducted in a 7.0‐T horizontal‐bore magnetic resonance scanner. The 19F‐MRI in rTg4510 mice showed an intense signal in the forebrain region. Analysis of the signal intensity in the forebrain region revealed a significant accumulation of fluorine‐19 magnetic resonance signal in the rTg4510 mice compared with the wild‐type mice. Histological analysis showed fluorescent signals of Shiga‐X35 binding to the NFTs in the brain sections of rTg4510 mice. Data collected as part of this investigation indicate that 19F‐MRI using Shiga‐X35 could be a promising tool to evaluate tau pathology in the brain.

TAU IMAGING USING FLUORINE-19 MRI IN A MOUSE MODEL OF TAUOPATHY

of neuroticism, extroversion, openness, agreeableness, and conscientiousness and underwent [18F]-AV-1451 tau-PET and [18F]-AV-45 b-amyloid-PET imaging. Tau levels were assessed in four regions including the amygdala, entorhinal cortex, inferior temporal cortex, and lateral occipital cortex (Figure 1), which are known to display early tau accumulation in AD. b-amyloid was examined as a composite measure from previously well-defined AD-related regions. We utilized linear regression models, adjusting for age and sex, to evaluate the association between the each of the personality traits and regional tau accumulation. Secondary analyses additionally adjusted for b-amyloid deposition. Results: Elevated neuroticism scores were significantly associated with higher tau accumulation in the amygdala (p1⁄4.003), entorhinal cortex (p1⁄4.031), and inferior temporal cortex (p<.001) (Figure 2a). In contrast, extroversion, openness, agreeableness, and conscientiousness were not associated with tau deposition for any of these regions (Figure 2b-e). After additionally adjusting for b-amyloid, results remained essentially unchanged (Table 1). Conclusions: Our results indicate that

APPLICATION OF DOUBLE MR IMAGING TO DETECT AMYLOID OLIGOMERS IN THE BRAIN OF APP/PS1 TRANSGENIC MODEL MICE

IC-P-031 APPLICATION OF DOUBLE MR IMAGING TO DETECTAMYLOID OLIGOMERS IN THE BRAIN OFAPP/PS1 TRANSGENIC MODEL MICE Ikuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi, Tomoko Kato, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Shigehiro Morikawa, Shiga University of Medical Science, Otsu, Japan; Northeastern Industrial Research Center of Shiga Prefecture, Nagahama, Japan; Industrial Research Center of Shiga Prefecture, Nagahama, Japan; Otsuka Pharmaceutical Co., Ltd, Kawauchi-cho, Japan. Contact e-mail: kinchan@belle.shiga-med.ac.jp

A NOVEL 19F MRI PROBE FOR DETECTING AMYLOID DEPOSITION IN ALZHEIMER'S DISEASE

Claudio Cuello, Pedro Rosa-Neto, McGill Center for Studies in Aging, Montreal, Quebec, Canada; McGill Centre for Studies in Aging, Montreal, Quebec, Canada; Biospective Inc., Montreal, Quebec, Canada; McGill Center for Studies in Aging, Montreal, Quebec, Canada; Montreal Neurological Institute, Montreal, Quebec, Canada; McGill Center for Studies for Aging,Montreal, Quebec, Canada; McGill Center for Studies in Aging, Montreal, Quebec, Canada; McGill University, Montreal, Quebec, Canada; McGill Center for Studies in Aging, Porto Alegre, Brazil. Contact e-mail: erzimmer@gmail.com

Required features of a fluorine-19 MRI probe for amyloid detection in the brain

(Fe), copper (Cu), and zinc (Zn). The overall levels of these metals have been investigated in a variety of brain homogenates and extracts, unfortunately these analyses have provided little consensus on the importance of the overall levels in Alzheimer’s disease. While this is the case, specific regions of enrichment, or mis-localisation of metals in the Alzheimer’s disease brain are very important and by attenuating a specific metal such that it does not interact with Ab should provide a therapeutic benefit. Methods: Brain tissue samples of 18 month old PPSAPP mouse were used for this study. The localization of amyloid plaques was determined by staining the tissue sections with Thioflavin S. The concentration and distribution of trace elements in the brain tissue were measured with x-ray florescence microprobe. The experiments were carried out at beamline XFM at the Australian Synchrotron. Results: Using the PSAPP mouse model of cerebral amyloid plaque formation, we conducted a survey ofmetal ion content and distribution Ca, Fe, Cu, and Zn through the neocortex and hippocampus using XFM. We established that elastic scattering and differential phase contrast can be used to identify the location of plaques without the need for typical histological staining. Plaque metalliation levels varied in concert with the metal content of the surrounding neutrophil and within a given anatomical region was found to be highly uniform across many tens of aggregates. Conclusions: Since neuropathological changes in human Alzheimer’s disease are presumed to involve disturbances to metal physiology, quantification of statistical representative numbers of plaques without the need for staining before assay promises to provide insight into the pathogenesis of Alzheimer’s disease.