Natalizumab alters the TCR repertoire after one year of treatment in four MS patients

International audiencen.

Gpr158 mediates osteocalcin's regulation of cognition

That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether OCN is also sufficient to improve these behaviors in wild-type mice, when circulating levels of OCN decline as they do with age. Here we show that the presence of OCN is necessary for the beneficial influence of plasma from young mice when injected into older mice on memory and that peripheral delivery of OCN is sufficient to improve memory and decrease anxiety-like behaviors in 16-mo-old mice. A second question is to identify a receptor transducing OCN signal in neurons. Genetic, electrophysiological, molecular, and behavioral assays identify Gpr158, an orphan G protein-coupled receptor expressed in neurons of the CA3 region of the hippocampus, as transducing OCN's regulation of hippocampal-dependent memory in part through inositol 1,4,5-trisphosphate and brain-derived neurotrophic factor. These results indicate that exogenous OCN can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes

Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc)-null mice: evidence for a critical role of the central nervous system

<p>Abstract</p> <p>Background</p> <p>The cellular prion protein (PrPc) is a host-encoded glycoprotein whose transconformation into PrP scrapie (PrPSc) initiates prion diseases. The role of PrPc in health is still obscure, but many candidate functions have been attributed to the protein, both in the immune and the nervous systems. Recent data show that experimental autoimmune encephalomyelitis (EAE) is worsened in mice lacking PrPc. Disease exacerbation has been attributed to T cells that would differentiate into more aggressive effectors when deprived of PrPc. However, alternative interpretations such as reduced resistance of neurons to autoimmune insult and exacerbated gliosis leading to neuronal deficits were not considered.</p> <p>Method</p> <p>To better discriminate the contribution of immune cells versus neural cells, reciprocal bone marrow chimeras with differential expression of PrPc in the lymphoid or in the central nervous system (CNS) were generated. Mice were subsequently challenged with MOG_35-55peptide and clinical disease as well as histopathology were compared in both groups. Furthermore, to test directly the T cell hypothesis, we compared the encephalitogenicity of adoptively transferred PrPc-deficient versus PrPc-sufficient, anti-MOG T cells.</p> <p>Results</p> <p>First, EAE exacerbation in PrPc-deficient mice was confirmed. Irradiation exacerbated EAE in all the chimeras and controls, but disease was more severe in mice with a PrPc-deleted CNS and a normal immune system than in the reciprocal construction. Moreover, there was no indication that anti-MOG responses were different in PrPc-sufficient and PrPc-deficient mice. Paradoxically, PrPc-deficient anti-MOG 2D2 T cells were less pathogenic than PrPc-expressing 2D2 T cells.</p> <p>Conclusions</p> <p>In view of the present data, it can be concluded that the origin of EAE exacerbation in PrPc-ablated mice resides in the absence of the prion protein in the CNS. Furthermore, the absence of PrPc on both neural and immune cells does not synergize for disease worsening. These conclusions highlight the critical role of PrPc in maintaining the integrity of the CNS in situations of stress, especially during a neuroinflammatory insult.</p

Gender and sex hormones in multiple sclerosis pathology and therapy

Several lines of evidence indicate that gender affects the susceptibility and course of multiple sclerosis (MS) with a higher disease prevalence and overall better prognosis in women than men. This sex dimorphism may be explained by sex chromosome effects and effects of sex steroid hormones on the immune system, blood brain barrier or parenchymal central nervous system (CNS) cells. The well known improvement in disease during late pregnancy has also been linked to hormonal changes and has stimulated recent clinical studies to determine the efficacy of and tolerance to sex steroid therapeutic approaches. Both clinical and experimental studies indicate that sex steroid supplementation may be beneficial for MS. This could be related to anti-inflammatory actions on the immune system or CNS and to direct neuroprotective properties. Here, clinical and experimental data are reviewed with respect to the effects of sex hormones or gender in the pathology or therapy of MS or its rodent disease models. The different cellular targets as well as some molecular mechanisms likely involved are discussed

Hubungan antara tipe kepribadian (ekstrovert dan introvert) dengan kebermaknaan hidup (meaning of life) pada mahasiswa Fakultas Psikologi UIN Maulana Malik Ibrahim Malang

INDONESIA: Setiap orang selalu berbeda dalam keinginan, motivasi, tujuan, cita-cita, nilai hidup, kebutuhan, dan alasan. Demikian juga mahasiswa Psikologi UIN Maulana Malik Ibrahim Malang memiliki tujuan, cita-cita, dan nilai hidup yang berbeda-beda, karena mahasiswa psikologi mempunyai tipe kepribadian yang berbeda-beda. Tipe kepribadian tersebut dibagi menjadi2, tipe kepribadian ekstrovert dan tipe kepribadian introvert. Penelitian ini bertujuan untuk: (1) untuk mengetahui tingkat kebermaknaan hidup (meaning of life) pada Mahasiswa Fakultas Psikologi (2) untuk mengetahui tipe kepribadian (ekstrovert dan introvert) mahasiswa Fakultas Psikologi (3) untuk mengetahui hubungan antara tipe kepribadian (ekstrovert dan introvert) dengan kebermaknaan hidup (meaning of life) mahasiswa Fakultas Psikologi. Penelitian ini dilakukan pada mahasiswa Psikologi angkatan 2008-2011 dengan menggunakan rancangan penelitian kuantitatif korelasi. Sampel penelitian diambil 15% dari 652 mahasiswa menjadi 99 mahasiwa. Pengambilan sampel menggunakan purposive sampling dengan kriteria sebagai berikut: Mahsiswa angkatan 2008-2011, masih aktif kuliah, dan berada pada usia dewasa awal antara 18-25tahun. Pengambilan data menggunakan alat tes dan skala sikap kebermaknaan hidup. Pada pengolahan data menggunakan Product Moment Correlation dari Pearson, dan uji validitas serta realibilitas memakai Alpha Cronbach. Pengolahan data tersebut diolah dengan program SPSS 16.0 for Windows. Hasil penelitian menunjukkan bahwa tipe kepribadian yang dominan pada mahasiswa psikologi adalah tipe kepribadian ekstrovert sebanyak 86 mahasiswa (86,87%) dan tipe kepribadian introvert sebanyak 13 mahasiswa (13,13%). Sedangkan pada variabel kebermaknaan hidup diperoleh hasil bahwa tingkat kebermaknaan hidup mahasiswa berada dalam kategori tinggi sebesar 80,8% kategori sedang memiliki prosentase 18,2%, dan kategori rendah sebesar 1%. Pada hasil analisis data, menunjukkan bahwa tidak ada hubungan antara tipe kepribadian (ekstrovert dan introvert) dengan kebermaknaan hidup. karena nilai korelasi (rxy) adalah positif 0,187. Dengan perolehan p hitung = 0,064 > 0,05 yang menandakan bahwa hubungan yang terjadi adalah tidak signifikan. ENGLISH: Everyone is always different in the desire, motivation, goals, ideals, values of life, needs, and reason. Similarly, Psychology student UIN Malang Maulana Malik Ibrahim has goals, ideals, and values are different, because psychology students have the personality type that is different. Personality types are divided menjadi2, extroverted personality types and introvert personality type. This study aimed to: (1) to determine the level of meaningfulness of life (meaning of life) at the Faculty of Psychology Students (2) to determine the type of personality (extrovert and introvert) Faculty of Psychology (3) to determine the relationship between personality types (extroverts and introverts ) with the meaningfulness of life (meaning of life) students of the Faculty of Psychology. The research was conducted in 2008-2011 with a psychology student generation using quantitative correlation study design. The samples taken 15% of 652 students to 99 students. Sampling using a purposive sampling with the following criteria: Mahsiswa Force 2008-2011, was active in college, and is in early adulthood between 18-25tahun. Retrieval of data using a test and attitude scale meaningfulness of life. On data processing use of Pearson Product Moment Correlation, and test the validity and reliability using Cronbach Alpha. Processing the data was processed with SPSS 16.0 for Windows. The results showed that the dominant personality types in psychology students are extroverted personality type as much as 86 students (86.87%) and introverted personality type as many as 13 students (13.13%). While on the meaningfulness of life variables obtained results that the meaningfulness of life of students are in high category is the category of 80.8% have a percentage of 18.2%, and low categories of 1%. On the results of data analysis, showed that there was no relationship between personality types (extroverts and introverts) with the meaningfulness of life. because the value of the correlation (rxy) is positive 0.187. With the acquisition count = 0.064 p> 0.05, indicating that the relationship that occurs is not significant

L'astrocyte réactif comme cible directe des estrogènes au cours de la neuro-inflammation auto-immune

PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Sex steroids and neuroprotection in spinal cord injury: A review of preclinical investigations

International audienceSpinal cord injury (SCI) is a debilitating condition that affects motor, sensory and autonomic functions. Subsequent to the first mechanical trauma, secondary events, which include inflammation and glial activation, exacerbate tissue damage and worsen functional deficits. Although these secondary injury mechanisms are amenable to therapeutic interventions, the efficacy of current approaches is inadequate. Further investigations are necessary to implement new therapies that can protect neural cells and attenuate some of the detrimental effects of inflammation while promoting regeneration. Studies on different animal models of SCI indicated that sex steroids, especially 17β-estradiol and progesterone, exert neuroprotective, anti-apoptotic and anti-inflammatory effects, ameliorate tissue sparing and improve functional deficits in SCI. As sex steroid receptors are expressed in a variety of cells including neurons, glia and immune system-related cells which infiltrate the injury epicenter, sex steroids could impact multiple processes simultaneously and in doing so, influence the outcomes of SCI. However, the translation of these pre-clinical findings into the clinical setting presents challenges such as the narrow therapeutic time window of sex steroid administration , the diversity of treatment regimens that have been employed in animal studies and the lack of sufficient information regarding the persistence of the effects in chronic SCI. The current review will summarize some of the major findings in this field and will discuss the challenges associated with the implementation of sex steroids as a promising treatment in human SCI