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In vivo H MR spectroscopy allows the non invasive characterization of brain metabolites and it has been used for studying brain metabolic changes in a wide range of neurodegenerative diseases. The prion diseases form a group of fatal neurodegenerative diseases, also described as transmissible spongiform encephalopathies. The mechanism by which prions elicit brain damage remains unclear and therefore different transgenic mouse models of prion disease were created. We performed an in vivo longitudinal H MR spectroscopy study at 14.1 T with the aim to measure the neurochemical profile of Prnp -/- and PrP mice in the hippocampus and cerebellum. Using high-field MR spectroscopy we were able to analyze in details the in vivo brain metabolites in Prnp -/- and PrP mice. An increase of myo-inositol, glutamate and lactate concentrations with a decrease of N-acetylaspartate concentrations were observed providing additional information to the previous measurements. [ABSTRACT FROM AUTHOR]

Inclusion body myositis (IBM), the most common inflammatory myopathy in the elderly, is often resistant to various forms of therapy. Placebo-controlled treatment trials with high dose intravenous immunoglobulins (IVIG) have shown disease amelioration in some but not all patients. Here, we present the informative case of a 70-year-old woman with diagnosed inclusion body myositis that showed progressive muscle weakness without treatment and following immuno-suppressive treatment with corticosteroids and azathioprine. A trial with low-dose intravenous immunoglobulins was started at that time. The patient responded rapidly to low dose IVIG treatment with amelioration of muscle strength and normalization of CK serum activities. Our results demonstrate that IBM patients may respond to low-dose IVIG treatment which has important clinical and economic consequences. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase 1 (IDH1) mutations are frequent in astrocytomas, oligoastrocytomas and oligodendrogliomas. We previously reported the generation of a mutation-specific antibody that specifically detects R132H mutated IDH1 protein (clone H09). Here, we investigate the feasibility of H09 immunohistochemistry to differentiate between oligodendrogliomas/oligoastrocytomas and other tumors with similar morphology. A total of 274 brain tumors presenting with focal or extensive clear cell morphology were investigated. High numbers of H09-positive cases were observed in adult grade II oligodendrogliomas (67 of 74, 91%), grade III oligodendrogliomas (65 of 69, 94%), grade II oligoastrocytomas (11 of 14, 79%) and grade III oligoastrocytomas (10 of 11, 91%). All cases of pediatric oligodendrogliomas (n = 7), neurocytomas (n = 41, 35 central, 4 extraventricular, 2 cerebellar liponeurocytomas), dysembryoplastic neuroepithelial tumors (n = 21), clear cell ependymomas (n = 8), clear cell meningiomas (n = 9) as well as 12 primary glioblastomas with oligodendroglial differentiation and 5 pilocytic astrocytomas with oligodendroglial- like differentiation were negative for H09 immunohistochemistry. Three oligodendrogliomas with neurocytic differentiation had evidence of IDH1/IDH2 mutations either by H09 immunohistochemistry or direct sequencing. We conclude that in tumors with an oligodendroglioma- like morphology, binding of H09 is highly specific for oligodendrogliomas or oligoastrocytomas and substantially helps in the discrimination from other clear cell tumors. Negative H09 immunohistochemistry of an adult oligodendroglioma or oligoastrocytoma should prompt the consideration of other clear cell neoplasms. Further, our observations firmly assign oligodendrogliomas with neurocytic differentiation to the group of oligodendrogliomas and demonstrate that H09 is especially helpful for the difficult discrimination of such lesions from extraventricular neurocytomas. [ABSTRACT FROM AUTHOR]

The integrity of peripheral nerves relies on communication between axons and Schwann cells. The axonal signals that ensure myelin maintenance are distinct from those that direct myelination and are largely unknown. Here we show that ablation of the prion protein PrPC triggers a chronic demyelinating polyneuropathy (CDP) in four independently targeted mouse strains. Ablation of the neighboring Prnd locus, or inbreeding to four distinct mouse strains, did not modulate the CDP. CDP was triggered by depletion of PrPC specifically in neurons, but not in Schwann cells, and was suppressed by PrPC expression restricted to neurons but not to Schwann cells. CDP was prevented by PrPC variants that undergo proteolytic amino-proximal cleavage, but not by variants that are nonpermissive for cleavage, including secreted PrPC lacking its glycolipid membrane anchor. These results indicate that neuronal expression and regulated proteolysis of PrPC are essential for myelin maintenance. [ABSTRACT FROM AUTHOR]

To reconnect with their synaptic targets, severed axons need to regrow robustly and directionally along the pre-lesional trajectory. While mechanisms directing axonal regrowth are poorly understood, several proteins direct developmental axon outgrowth, including the ubiquitin ligase PHR (Mycbp2). Invertebrate PHR also limits regrowth of injured axons, whereas its role in vertebrate axonal regrowth remains elusive. Here we took advantage of the high regrowth capacity of spinal zebrafish axons and observed robust and directional regrowth following laser transection of spinal Mauthner axons. We found that PHR directs regrowing axons along the pre-lesional trajectory and across the transection site. At the transection site, initial regrowth of wild-type axons was multidirectional. Over time, misdirected sprouts were corrected in a PHR-dependent manner. Ablation of cyfip2, known to promote F-actin-polymerization and pharmacological inhibition of JNK reduced misdirected regrowth of PHR-deficient axons, suggesting that PHR controls directional Mauthner axonal regrowth through cyfip2- and JNK-dependent pathways. Juliane Bremer et al. show that ubiquitin ligase PHR directs the regrowth of zebrafish Mauthner axons after transection. Misdirected axonal regrowth caused by the lack of PHR can be reversed by pharmacological inhibition of JNK or genetic ablation of cyfip2, suggesting an important role for these signaling pathways in spinal axonal regrowth. [ABSTRACT FROM AUTHOR]