Dr Panayiota Poirazi, chair of the FENS-Kavli Network of Excellence, analyzes the problems that european early- and mid-career scientists must face everyday as they try to obtain research funds, also suggesting the mechanisms of grant application and evaluation that funding agencies should improve to help young scientists build a career.
La Fondazione italiana sclerosi multipla ha pubblicato il Bando FISM 2017 per il finanziamento di progetti di ricerca e borse di studio sulla sclerosi multipla.
In this review, recently published on Science, Dr. Jonathan Kipnis summarizes the cellular and molecular mechanisms behind the role of lymphocytes in inducing and modulating immune tolerance in the CNS, with particular attention to the trafficking of immune cells and solubile factors throughout the meningeal lymphatic vessels and peripheral deep cervical lymph nodes.
L’importante finanziamento assegnato al neurologo Gianvito Martino (San Raffaele) per un progetto di ricerca che coinvolge laboratori tra Europa, Stati Uniti e Canada
Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection...
J Exp Med.; 2016
A newly updated map of the human brain may be the most accurate yet, helping solve over 100 years of arguments.
Nature; August 2016
Myasthenia gravis (MG) is a chronic autoimmune disease characterized by fluctuating muscle weakness, which, in the majority of patients, is treated with corticosteroids. In a recently published clinical trial, 50 patients with generalized MG were randomly assigned to prednisone + methotrexate or prednisone + placebo. The amount of prednisone that…
Increasing evidence suggests that neuro-immune and neuro-glial interactions are critically involved in chronic pain sensitization. It is well studied how immune/glial mediators sensitize pain, but how sensory neurons control neuroinflammation remains unclear. We employed Myd88 conditional knockout (CKO) mice, in which Myd88 was deleted in sodium channel subunit Nav1.8-expressing primary sensory neurons, to examine the unique role of neuronal MyD88 in regulating acute and chronic pain, and possible underlying mechanisms. We found that ...
Severe viral infection during pregnancy has been linked to increased risk of autism spectrum disorder (ASD) in offspring. Now, a study in mice shows that ASD-like behaviour in offspring in response to maternal immune activation depends on maternal CD4+T cells expressing retinoic acid receptor-related orphan receptor-γt (RORγt) and interleukin-17A…
Tissue macrophages are highly heterogeneous populations that are shaped by the signals they encounter in their surrounding environment. Mucida and colleagues have used a range of imaging techniques to detail key differences between the macrophages found in the lamina propria of the small intestine and those that reside in the underlying muscularis layers.
A previously unknown mechanism contributes to dysfunction of the neurogenic niche during CNS autoimmunity. Natural killer cells are retained specifically in the subventricular zone in chronic disease, killing stem cells and promoting pathology.
Motor neurons are the final stage of neural processing for the execution of motor behaviours. Traditionally, motor neurons have been viewed as the ‘final common pathway’, serving as passive recipients merely conveying to the muscles the final motor program generated by upstream interneuron circuits1, 2. Here we reveal an unforeseen role of motor neurons in controlling the locomotor circuit function via gap junctions in zebrafish. These gap junctions mediate a retrograde analogue propagation of voltage fluctuations from motor neurons to control the synaptic release and recruitment of the upstream V2a interneurons that drive locomotion. Selective inhibition of motor neurons during ongoing locomotion de-recruits V2a interneurons and strongly influences locomotor circuit function. Rather than acting as separate units, gap junctions unite motor neurons and V2a interneurons into functional ensembles endowed with a retrograde analogue computation essential for locomotor rhythm generation. These results show that motor neurons are not a passive recipient of motor commands but an integral component of the neural circuits responsible for motor behaviour.
Glutamate receptors form complexes in the brain with auxiliary proteins, which control their activity during fast synaptic transmission through a seemingly bewildering array of effects. Here we devise a way to isolate the activation of complexes using polyamines, which enables us to show that transmembrane AMPA receptor regulatory proteins (TARPs) exert their effects principally on the channel opening reaction. A thermodynamic argument suggests that because TARPs promote channel opening, receptor activation promotes AMPAR-TARP complexes into a superactive state with high open probability. A simple model based on this idea predicts all known effects of TARPs on AMPA receptor function. This model also predicts unexpected phenomena including massive potentiation in the absence of desensitization and supramaximal recovery that we subsequently detected in electrophysiological recordings. This transient positive feedback mechanism has implications for information processing in the brain, because it should allow activity-dependent facilitation of excitatory synaptic transmission through a postsynaptic mechanism.
Amyloid-like protein aggregation is associated with neurodegeneration and other pathologies. The nature of the toxic aggregate species and their mechanism of action remain elusive. Here, we analyzed the compartment specificity of aggregate toxicity using artificial β-sheet proteins, as well as fragments of mutant huntingtin and TAR DNA binding protein–43 (TDP-43). Aggregation in the cytoplasm interfered with nucleocytoplasmic protein and RNA transport. In contrast, the same proteins did not inhibit transport when forming inclusions in the nucleus at or around the nucleolus. Protein aggregation in the cytoplasm, but not the nucleus, caused the sequestration and mislocalization of proteins containing disordered and low-complexity sequences, including multiple factors of the nuclear import and export machinery. Thus, impairment of nucleocytoplasmic transport may contribute to the cellular pathology of various aggregate deposition diseases.
Astrocytes constitute a major proportion of cells in the hippocampal neurogenic niche, where they regulate neurogenesis through the release of soluble factors. However, the role of astrocytes in the synaptogenesis and integration of adult-born neurons into existing circuits is unknown. In this study, Sultan et al. show that astrocytes in the adult mouse neurogenic niche..
The DNA-repair protein BRCA1 is known to increase the risk of breast and ovarian cancer when it is mutated. But the normal protein might also have a central role in Alzheimer's disease. Elsa Suberbielle and Lennart Mucke at the Gladstone Institute of Neurological Disease in San Francisco, California, and their colleagues…
A randomized, double-blind, phase III trial of generic glatiramer acetate has shown equivalent efficacy and safety compared with the approved formulation, Copaxone. The impact of approval of generic glatiramer acetate, however, will mainly depend on the pricing of the drug.
Otchy et al. 2 compared the effects of acute and chronic manipulations of neural circuits on a specific behaviour. a, The authors taught rats to perform a complex ...
La scoperta che una rara malattia dai sintomi simili al Parkinson è causata da un prione rafforza l'ipotesi che all'origine di molte patologie neurodegenerative vi siano queste particelle proteiche mal ripiegate.
Alcuni scienziati sostengono di aver scoperto un nuovo prione umano, il primo dopo quasi cinquant'anni. I prioni sono proteine ripiegate in modo errato che fanno copie di se stesse inducendo altre proteine simili a deformarsi. Così facendo, si moltiplicano e causano malattie. In questo caso la malattia è l'atrofia multisistemica (MSA, nota anche come sindrome di Shy-Drager), una patologia neurodegenerativa simile al morbo di Parkinson. Lo studio, pubblicato il 31 agosto sui “Proceedings of the National Academy of Sciences”, rinvigorisce l'idea secondo cui molte malattie neurodegenerative siano causate da prioni.
More than two hundred individuals developed Creutzfeldt–Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions1,2. Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36–51 years, in four we found moderate to severe grey matter and vascular amyloid-b (Ab) pathology.
Brain plaques may have been seeded by contaminated hormone extracts from cadavers.
Nature - 09 September 2015
Only a decade ago, the idea that Alzheimer’s disease might be transmissible between people would have been laughed off the stage. But scientists have since shown that tissues can transmit symptoms of the disease between animals — and new results imply that humans, at least in one unusual circumstance, may not be an exception.
Investigators at sites worldwide are recruiting 375 people with primary-progressive MS for a Phase 2 clinical trial comparing oral laquinimod (Teva Pharmaceuticals), an experimental compound that is believed to modify immune function, with inactive placebo in 375 people with primary-progressive MS. The study is funded by Teva Pharmaceutical Industries Ltd.
University of Virginia scientists led by Dr. Jonathan Kipnis have uncovered evidence of a previously unrecognized network of vessels that facilitate immune system activity in the brain. The team showed evidence of this system, a network of “lymphatic vessels,” in both mice and people. This is a potentially groundbreaking discovery. Further research is needed to understand how and whether lymphatic vessels play a role in multiple sclerosis, and whether their existence presents new opportunities for stopping immune attacks involved in MS.
After a string of failed trials, drugs that target protein build-up in the brain appear to slow disease progress.
After years of disappointment, clinical-trial results released on 22 July suggest that antibody treatments may produce small improvements in people with Alzheimer’s disease.
The drugs — Eli Lilly’s solanezumab and Biogen’s aducanumab — target the amyloid-β protein that accumulates in the brains of people with Alzheimer’s. Many researchers question whether the findings will hold up, given that antibody drugs against amyloid have failed in every previous test against the disease. Details of the results were presented at the Alzheimer's Association International Conference in Washington DC.
Missense mutations in the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing family of gene 12 (Nlrp12) are associated with periodic fever syndromes and atopic dermatitis in humans. Here, we have demonstrated a crucial role for NLRP12 in negatively regulating pathogenic T cell responses. Nlrp12(-/-) mice responded to antigen immunization with hyperinflammatory T cell responses.
The antiinflammatory activity of intravenous immunoglobulin (IVIG) is dependent on the presence of sialic acid in the core IgG fragment crystallizable domain (Fc) glycan, resulting in increased conformational flexibility of the CH2 domain with corresponding modulation of Fc receptor (FcR) binding specificity from type I to type II receptors.
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). While etiology of the disease remains unknown, genetic susceptibility and autoimmune mechanisms in the initiation and progression of the disease have been strongly suggested.