Neuroscience

Nuclear pores: the gate to neurodegeneration

Nature Neuroscience - 25 January 2018 - 12:00am

Nuclear pores: the gate to neurodegeneration

Nuclear pores: the gate to neurodegeneration, Published online: 25 January 2018; doi:10.1038/s41593-017-0066-0

Compromised compartmentalization of nucleus and cytoplasm has emerged as a central feature of aging and neurodegenerative diseases. Nucleocytoplasmic transport is disrupted, with widespread mislocalization of nuclear pore proteins, in TDP-43 proteinopathies such as, amyotrophic lateral sclerosis and frontotemporal dementia.
Categories: Neuroscience

Issue Information - TOC

Annals of Neurology - 24 January 2018 - 7:03pm
Categories: Neuroscience

Annals of Neurology: Volume 83, Number 1, January 2018

Annals of Neurology - 24 January 2018 - 7:02pm

Antibodies against contactin associated protein-like 2 (Caspr2) are found in some patients with autoimmune encephalitis. To see how these antibodies interact with Caspr2, cultured rat hippocampal neurons were stained with antibodies against the Caspr2 protein on the cell surface (red) and with antibodies against the Caspr2 protein that can penetrate the cell (green). Nearly all of the stained protein is golden colored (overlap of red and green), indicating that it was stained with both antibodies because it was on the surface of the cell. Caspr2 antibodies may cause encephalitis by binding to nerve cells in the brain and blocking their cell surface interactions with other cells. See Patterson et al., pages 40–51, this issue.

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Issue Information - Copyright

Annals of Neurology - 24 January 2018 - 7:02pm
Categories: Neuroscience

Issue Information - Masthead

Annals of Neurology - 24 January 2018 - 7:02pm
Categories: Neuroscience

Diagnostic criteria for disorders of arousal: A video-polysomnography assessment

Annals of Neurology - 23 January 2018 - 5:41pm
ABSTRACT

Study objectives:

To assess video-polysomnographic (vPSG) criteria and their cut-off values for the diagnosis of disorders of arousal (DOA; sleepwalking, sleep terror).

Methods:

One hundred and sixty adult patients with DOA and 50 sex- and age-matched healthy participants underwent a clinical evaluation and vPSG assessment to quantify slow wave sleep (SWS) interruptions (SWS fragmentation index; slow/mixed and fast arousal ratios and indexes per hour) and the associated behaviors. First, a case-control analysis was performed in 100 patients and the 50 controls to define the optimal cut-off values using receiver operating characteristic curves. Their sensitivity was then assessed in the other 60 patients with DOA.

Results:

The SWS fragmentation index and the mixed, slow, slow/mixed arousal indexes and ratios were higher in patients with DOA than controls. The highest area under the curve (AUC) values were obtained for the SWS fragmentation and slow/mixed arousal indexes (AUC = 0.88 and 0.90, respectively). The SWS fragmentation index cut-off value of 6.8/h reached a sensitivity of 79% and a specificity of 82%. The slow/mixed arousal index had a sensitivity of 94% for the 2.5/h cut-off, and 100% specificity for 6/h. Both parameters showed good inter-rater agreement, and their sensitivities were confirmed in the second group of patients. Combining EEG parameters and video-based behavioral analyses increased the correct classification rate up to 91.3%.

Conclusion:

Frequent slow/mixed arousals in SWS and complex behaviors during vPSG are strongly associated with DOA, and could be promising biomarkers for the diagnosis of non-REM parasomnias. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

A Mendelian form of neural tube defect caused by a de novo null variant in SMARCC1 in an identical twin

Annals of Neurology - 23 January 2018 - 5:40pm
ABSTRACT

Neural tube defects (NTD) are among the most common birth defects in humans and yet their molecular etiology remains poorly understood. NTD are believed to result from the complex interaction of environmental factors with a multitude of genetic risk factors in a classical multifactorial disease model. Mendelian forms of NTD in which single variants are sufficient to cause the disease are extremely rare. We report a monozygotic twin with severe NTD (occipital encephalocele and myelomeningocele) and a shared de novo likely truncating variant in SMARCC1. RTPCR analysis suggests the potential null nature of the variant due to NMD. SMARCC1 is extremely constrained in humans and encodes a highly conserved core chromatin remodeler BAF155. Mice that are heterozygous for a null allele or homozygous for a hypomorphic allele develop severe NTD in the form of exencephaly. This is the first report of SMARCC1 mutation in humans and it shows a critical and conserved requirement for intact BAF chromatin remodeling complex in neurulation. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Inhibitory circuit gating of auditory critical-period plasticity

Nature Neuroscience - 22 January 2018 - 12:00am

Inhibitory circuit gating of auditory critical-period plasticity

Inhibitory circuit gating of auditory critical-period plasticity, Published online: 22 January 2018; doi:10.1038/s41593-017-0064-2

The authors show that inhibitory interneurons in cortical layer 1 integrate topographically organized thalamic and neuromodulatory inputs to sculpt sound frequency maps in primary auditory cortex during a developmental critical period.
Categories: Neuroscience

Randomized trial of transcranial DC stimulation for post-stroke dysphagia

Annals of Neurology - 19 January 2018 - 5:40pm
Abstract

Objective: We evaluated whether transcranial direct current stimulation (tDCS) is able to enhance dysphagia rehabilitation following stroke. Besides relating clinical effects with neuroplastic changes in cortical swallowing processing we aimed to identify factors influencing treatment success.

Methods: In this double-blind, randomized study 60 acute dysphagic stroke patients received contralesional anodal (1 mA, 20 min) or sham tDCS on four consecutive days. Swallowing function was thoroughly assessed before and after the intervention using the validated Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and clinical assessment. In 10 patients, swallowing-related brain activation was recorded applying magnetoencephalography (MEG) before and after the intervention. Voxel-based statistical lesion pattern analysis was also performed.

Results: Study groups did not differ according to demographic data, stroke characteristics, or baseline dysphagia severity. Patients treated with tDCS showed greater improvement in FEDSS than the sham group (1.3 vs 0.4 points, mean difference: 0.9 [95%CI 0.4–1.4], p<0.0005). Functional recovery was accompanied by a significant increase of activation (p<0.05) in the contralesional swallowing network after real but not sham tDCS. Looking for predictors of treatment success every hour of earlier treatment initiation was associated with greater improvement of FEDSS (adjusted OR 0.99 [0.98–1.00], p<0.05) in multivariable analysis. Stroke location in the right insula and operculum was indicative of worse response to tDCS (p<0.05).

Interpretation: Application of tDCS over the contralesional swallowing motor cortex supports swallowing network reorganization, thereby leading to faster rehabilitation of acute post-stroke dysphagia. Early treatment initiation seems beneficial. TDCS may be less effective in right-hemispheric insulo-opercular stroke. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Neuroimmunology: Brain police

Nature Rev. Neurosc. - 19 January 2018 - 12:00am

Neuroimmunology: Brain police

Neuroimmunology: Brain police, Published online: 19 January 2018; doi:10.1038/nrn.2018.5

Microglial surveillance of the brain is dependent on maintenance of microglia membrane potential by the K+ channel THIK1, which is potentiated by ATP released at sites of tissue injury acting on P2Y12 receptors.
Categories: Neuroscience

Mitochondria at the neuronal presynapse in health and disease

Nature Rev. Neurosc. - 19 January 2018 - 12:00am

Mitochondria at the neuronal presynapse in health and disease

Mitochondria at the neuronal presynapse in health and disease, Published online: 19 January 2018; doi:10.1038/nrn.2017.170

Mitochondria may be actively recruited to presynapses to supply energy, buffer calcium and, potentially, fulfil other functions. In this Review, Devine and Kittler examine the importance of this presynaptic population of mitochondria in the maintenance of neuronal homeostasis and how dysfunctional presynaptic mitochondria might contribute to neurodegenerative diseases.
Categories: Neuroscience

Learning and memory: You only learn once

Nature Rev. Neurosc. - 19 January 2018 - 12:00am

Learning and memory: You only learn once

Learning and memory: You only learn once, Published online: 19 January 2018; doi:10.1038/nrn.2018.4

When mice explore a new context, neurons in the locus coeruleus that project to hippocampal regions CA3 enable the learning of the new environment.
Categories: Neuroscience

Neurodegenerative disease: A proteostatic boost

Nature Rev. Neurosc. - 19 January 2018 - 12:00am

Neurodegenerative disease: A proteostatic boost

Neurodegenerative disease: A proteostatic boost, Published online: 19 January 2018; doi:10.1038/nrn.2018.3

Amyloid-β (Aβ)-induced proteotoxicity is linked to a mitochondrial stress response that may be conserved across species, and promoting mitochondrial proteostasis counteracts Aβ aggregation in worms and an Alzheimer disease mouse model.
Categories: Neuroscience

Grid scale drives the scale and long-term stability of place maps

Nature Neuroscience - 15 January 2018 - 12:00am

Grid scale drives the scale and long-term stability of place maps

Grid scale drives the scale and long-term stability of place maps, Published online: 15 January 2018; doi:10.1038/s41593-017-0055-3

How entorhinal grid cells control hippocampal coding and behavior remains elusive. The authors report that increasing the spatial scale of grid cells expands the scale and reduces the stability of place fields, impairing spatial memory in mice.
Categories: Neuroscience

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice

Nature Neuroscience - 15 January 2018 - 12:00am

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice, Published online: 15 January 2018; doi:10.1038/s41593-017-0060-6

dCas9-mediated activation has been verified and widely used in vitro. Here the authors generated a potent in vivo activation platform and applied it to control the transcription of multiple genetic elements in the mammalian brain.
Categories: Neuroscience

Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing

Nature Neuroscience - 15 January 2018 - 12:00am

Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing

Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing, Published online: 15 January 2018; doi:10.1038/s41593-017-0056-2

Using single-cell RNA-seq, the authors show that early developmental neurogenesis in the dentate gyrus of the hippocampus is largely conserved in the adult, but with a perinatal transformation of stem cells to an adult type.
Categories: Neuroscience

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

Nature Neuroscience - 15 January 2018 - 12:00am

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response, Published online: 15 January 2018; doi:10.1038/s41593-017-0059-z

A salt-rich diet promotes cerebrovascular diseases and dementia. This study shows that high dietary salt in mice induces a TH17 response in the gut leading to cerebral endothelial dysfunction and cognitive impairment via circulating IL-17.
Categories: Neuroscience

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons

Nature Neuroscience - 15 January 2018 - 12:00am

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons, Published online: 15 January 2018; doi:10.1038/s41593-017-0061-5

Sasaki et al. reveal that the dentate gyrus not only performs pattern separation but also has a direct role in organizing memory-guided behavior by coordinating the planning of future actions.
Categories: Neuroscience

<i>N</i><sup>6</sup>-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications

Nature Neuroscience - 15 January 2018 - 12:00am

N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications

<i>N</i><sup>6</sup>-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications, Published online: 15 January 2018; doi:10.1038/s41593-017-0057-1

Using a genetic approach, Wang et al. demonstrate an essential function for m6A mRNA modification in promoting neural stem cell proliferation and reveal interactions between m6A and histone modification as a novel gene regulatory mechanism.
Categories: Neuroscience

Deep grey matter volume loss drives disability worsening in multiple sclerosis

Annals of Neurology - 13 January 2018 - 4:45pm
Abstract

Objective: Grey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.

Methods: We analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsing-remitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.

Results: SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; p<0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%)[p<0.01]. The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%) (all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta=0.04, p<0.001).

Interpretation: This large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

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