Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases

<p>Abstract</p> <p>Background</p> <p>Phospho-tau deposition has been described in a rare genetic human prion disease, Gerstmann-Sträussler-Scheinker syndrome, but is not common neuropathological picture for other human and animal transmissible spongiform encephalopathies (TSEs). This study investigated the possible changes of tau and phosphorylated tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in scrapie experimental animals.</p> <p>Methods</p> <p>The profiles of tau and p-tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in the brain tissues of agents 263K- or 139A-infected hamsters were evaluated by Western blots and real-time PCR. Meanwhile, the transcriptional and expressive levels of GSK3β and CDK5 in the brains were tested.</p> <p>Results</p> <p>The contents of total tau and p-tau at Ser202/Thr205 increased, but p-tau at Ser396 and Ser404 decreased at the terminal stages, regardless of scrapie strains. Transcriptional levels of two tau isoforms were also increased. Additionally, it showed higher CDK5, but lower GSK3β transcriptional and expressive levels in the brains of scrapie-infected animals. Analysis of brain samples collected from different times after inoculated with agent 263 K revealed that the changes of tau profiles and phosphate kinases were time-relative events.</p> <p>Conclusion</p> <p>These data suggest that changes of profiles of p-tau at Ser396, Ser404 and Ser202/Thr205 are illness-correlative phenomena in TSEs, which may arise of the alteration of phosphate kinases. Alteration of tau, p-tau (Ser396, Ser404, and Ser202/Thr205), GSK3β and CDK5 were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases.</p

Myosite focale : une maladie méconnue

International audienceFocal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual.Les myosites focales sont des maladies musculaires inflammatoires de cause inconnue. Elles se distinguent des autres myopathies auto-immunes par leur caractère limité à un muscle ou à un groupe musculaire, par l’absence de signe extramusculaire associé et par leur pronostic favorable en l’absence de traitement. Elles touchent le plus souvent le membre inférieur, et se présentent typiquement comme une masse plus ou moins douloureuse, sans déficit moteur associée. Le taux d’enzymes musculaires n’est pas élevé. L’IRM musculaire est l’élément diagnostique clef qui permet de voir une inflammation musculaire focale, touchant un seul muscle ou un groupe musculaire. Seule la biopsie musculaire permet d’affirmer le diagnostic, montrant des infiltrats inflammatoires sans topographie particulière constitués de lymphocytes et de macrophages associés le plus souvent à une expression focale de HLA-1 par les fibres musculaires. Elle permet surtout d’écarter des diagnostics différentiels comme un sarcome. Le pronostic est favorable avec une régression spontanée de la lésion en quelques semaines ou mois après les premiers symptômes. Les récidives sont possibles mais peu fréquentes

Clinical relevance of diffusion and perfusion magnetic resonance imaging in assessing intra-axial brain tumors

articleInternational audienceAdvanced magnetic resonance (MR) imaging techniques provide physiologic information that complements the anatomic information available from conventional MR imaging. We evaluated the roles of diffusion and perfusion imaging for the assessment of grade and type of histologically proven intraaxial brain tumors. A total of 28 patients with intraaxial brain tumors underwent conventional MR imaging (T2- and T1-weighted sequences after gadobenate dimeglumine injection), diffusion imaging and T2*-weighted echo-planar perfusion imaging. Examinations were performed on 19 patients during initial diagnosis and on nine patients during follow-up therapy. Determinations of relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were performed in the solid parts of each tumor, peritumoral region and contralateral white matter. For gliomas, rCBV values were greater in high-grade than in low-grade tumors (3.87+/-1.94 versus 1.30+/-0.42) at the time of initial diagnosis. rCBV values were increased in all recurrent tumors, except in one patient who presented with a combination of recurrent glioblastoma and massive radionecrosis on histology. Low-grade gliomas had low rCBV even in the presence of contrast medium enhancement. Differentiation between high- and low-grade gliomas was not possible using diffusion-weighted images and ADC values alone. In the peritumoral areas of untreated high-grade gliomas and metastases, the mean rCBV values were higher for high-grade gliomas (1.7+/-0.37) than for metastases (0.54+/-0.18) while the mean ADC values were higher for metastases. The rCBV values of four lymphomas were low and the signal intensity-time curves revealed a significant increase in signal intensity after the first pass of gadobenate dimeglumine. Diffusion and perfusion imaging, even with relatively short imaging and data processing times, provide important information for lesion characterization

A post-mortem study to compare the 5-HT1A receptor binding of a PET agonist and a PET antagonist in Alzheimer's disease

Présentation oraleInternational audienceAim. The 5-HT1A serotonin receptors located in hippocampus are known to be linked to memory processes. PET clinical imaging studies with [18F]MPPF have documented the decrease of 5-HT1A receptor expression in Alzheimer's disease patients, interpreted as neuronal loss. Interestingly, other [18F]MPPF PET studies have reported a specific increase in hippocampal 5-HT1A receptor binding during a pre-dementia stage of Alzheimer's disease (mild cognitive impairment). If this increase in [18F]MPPF binding may be explained by compensatory mechanisms, the pharmacological properties of this PET radiotracer limit its biological interpretation. It is known indeed that [18F]MPPF, which is an antagonist like a majority of available PET receptor radioligands, binds non-specifically to the high-affinity state of 5-HT1A receptors (functional) and to the low-affinity state of these receptors (decoupled from G proteins and non-functional). On the contrary, an agonist binds selectively to the high-affinity state of the receptor which are functional. The Aim of this study is demonstrate that the binding of a 5-HT1A PET agonist provides complementary information to the binding of a 5-HT1A PET antagonist, to improve understanding of the functional impairment of 5-HT1A receptors during Alzheimer's disease. Materials and MJethods. We compared in postmortem human brain sections the specific binding of [18F]F15599, a 5-HT1A PET agonist we developed previously, with the specific binding of [18F]MPPF, a 5-HT1A PET antagonist. Thirty-µm coronal sections were cut across hippocampi of 18 patients at different Braak's stages (from 0 to VI). The days of radiotracers synthesis, the brain slides were incubated in a saline buffer containing 37 kBq/mL of [18F]MPPF or [18F]F15599. Hippocampal subregions were drawn according to a brain atlas and binding quantification was performed with extemporaneous fluorine-18 scales. The specific binding of both radiotracers was determined by addition of 100 nM of serotonin and the agonist binding of [18F]F15599 was revealed by addition of 10 μM of Gpp(NH)p. Results and Conclusion. The autoradiography distribution of both 5-HT1A PET radiotracers varied across hippocampus regions. The highest binding density was found in the pyramidal layer of CA1, followed by the molecular layer of the dentate gyrus. The incubation with 10 μM of Gpp(NH)p, a non-hydrolysable analogue of GTP, reduced significantly [18F]F15599 binding, confirming its specific binding to G-coupled 5-HT1A receptors. [18F]F15599 binding compared to [18F]MPPF binding revealed specific modifications of the density of functional 5-HT1A correlated to the Braak's stages. These results justify an extension of this concept of functional PET imaging in clinical studies

Diffusion-weighted imaging in brain aspergillosis

articleBrain aspergillosis is a rare pathology, occurring mainly in immunocompromised patients, responsible for multiple cerebral septic infarctions. Some researchers have described magnetic resonance (MR) findings in cerebral invasive aspergillosis, but diffusion-weighted imaging (DWI) has rarely been reported, especially in typical non-enhancing lesions, while it may be helpful for early differential diagnosis and may allow earlier antifungal treatment. We describe three cases of patients presenting brain aspergillosis, with MR imaging including diffusion-weighted sequences and apparent diffusion coefficient (ADC) cartography. The three patients described in this study presented a total of 23 circular lesions, and one patient presented an infarction area in the territory of the right middle cerebral artery. Lesions were ring-enhancing for one patient, and presented no enhancement for the other two. Eleven lesions were very bright on DWI, with reduced ADC values. Twelve lesions, either enhancing or not enhancing, presented a 'target-like' aspect with central and peripheral hypointense areas on DWI, corresponding to higher ADC value areas, and intermediate marked hypersignal on DWI. This typical aspect of aspergillosis lesions on DWI may allow early diagnosis and treatment of cerebral aspergillosis, and is helpful for differentiating aspergillosis lesions from other infectious or malignant lesions affecting immunocompromised patients