Diseases of the nervous system articles within Nature Communications

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  • Article
    | Open Access

    Temporal lobe epilepsy can cause ionic imbalance in the brain and alter transcriptional activities. Here, van Loo et al.show that the increase in neuronal zinc following status epilepticus can induce transcriptional change via metal-regulatory transcription factor 1, and alter voltage-gated calcium channel CaV3.2 and intrinsic neuronal excitability.

    • Karen M. J. van Loo
    • , Christina Schaub
    •  & Albert J. Becker

  • Article
    | Open Access

    In Alzheimer's disease, tau spreads throughout the brain, however the nature of the tau species propagating from one neuron to another is not known. Here, Takeda et al. identify a rare, high-molecular-weight tau as the primary species taken up and transferred between synaptically connected neurons.

    • Shuko Takeda
    • , Susanne Wegmann
    •  & Bradley T. Hyman

  • Article
    | Open Access

    To maintain viability, cells must be able to sense and respond to mechanical stimuli. Here, Qi et al. show that the STOML3 protein acts in mechanosensation by binding cholesterol and regulating membrane stiffness which can in turn regulate ion flux through mechanosensitive channels.

    • Yanmei Qi
    • , Laura Andolfi
    •  & Jing Hu

  • Article
    | Open Access

    Myelin regeneration can occur spontaneously in demyelinating diseases but the underlying mechanisms are incompletely understood. Here the authors show that neuronal activity and glutamatergic synapses instruct oligodendrocyte progenitor cells to differentiate into new myelinating oligodendrocytes.

    • Hélène O. B. Gautier
    • , Kimberley A. Evans
    •  & Ragnhildur T Káradóttir

  • Article
    | Open Access

    Adult hippocampal neurogenesis is involved in the response to stress but whether it exerts a positive or negative effect remains unclear. Here the authors ablate hippocampal neurogenesis in mice and find that the effects on anxiety behaviour depend on the time of day, and that neurogenesis specifically impairs the response to stress during the dark cycle.

    • Cheng-Yu Tsai
    • , Ching-Yen Tsai
    •  & Guo-Jen Huang

  • Article
    | Open Access

    The potassium-chloride co-transporter, KCC2 is an essential component in maintaining a gradient for chloride ions in neurons. Here Stodberg and colleagues identify loss-of-function mutations in the encoding geneSLC12A5, which impair normal synaptic function associated with early-onset epilepsy.

    • Tommy Stödberg
    • , Amy McTague
    •  & Manju A. Kurian

  • Article
    | Open Access

    Long-chain omega-3 polyunsaturated fatty acids are essential for neural development and lack of these fatty acids has been implicated in a number of mental health conditions. Here the authors report the longer-term efficacy of a randomized, double-blind, placebo-controlled clinical trial assessing the effects of fish oil capsules in individuals at ultrahigh risk for psychosis.

    • G. Paul Amminger
    • , Miriam R. Schäfer
    •  & Patrick D. McGorry

  • Article
    | Open Access

    The sphingolipid sphingosine-1-phosphate (S1P) plays a vital role in vascular homeostasis through the interaction with its receptors S1PR1-5. Here, by using genetic and pharmacological approaches, the authors show that S1PR2-mediated signaling is crucial for the disruption of cerebrovascular integrity and development of intracerebral haemorrhage in a mouse stroke model.

    • Gab Seok Kim
    • , Li Yang
    •  & Teresa Sanchez

  • Article
    | Open Access

    Synapsins anchor synaptic vesicles (SVs) to the actin cytoskeleton to establish the reserve vesicle pool. Here Tanget al. show that SUMOylation of synapsin 1a enhances its interaction with SVs to promote efficient reclustering following stimulation, and a mutation linked to autism and epilepsy leads to defective SUMOylation.

    • Leo T. -H. Tang
    • , Tim J. Craig
    •  & Jeremy M. Henley

  • Article |

    CEP63 is a centrosomal protein that is mutated in the microcephaly disease Seckel syndrome. Here the authors disrupt Cep63 in the mouse and find that neural progenitor cells undergo p53-dependent cell death, and uncover a role for CEP63 in ensuring correct meiotic recombination in male gametes.

    • Marko Marjanović
    • , Carlos Sánchez-Huertas
    •  & Travis H. Stracker

  • Article |

    Abstinent smokers experience affective withdrawal symptoms that contribute to relapse, yet the circuitry and mechanisms underlying these symptoms are unknown. Here the authors identify a critical role for a ventral tegmental area-habenula-interpeduncular circuit in nicotine withdrawal-induced anxiety.

    • Rubing Zhao-Shea
    • , Steven R. DeGroot
    •  & Andrew R. Tapper

  • Article |

    Phagocytic glia can internalize protein aggregates in vitro. Here Pearce et al. show in Drosophila that glia clear mutant huntingtin (Htt) aggregates in a scavenger receptor Draper-dependent manner in vivo, and that internalized Htt aggregates induce the prion-like conversion of wild-type Htt expressed in the glial cytoplasm.

    • Margaret M. P. Pearce
    • , Ellen J. Spartz
    •  & Ron R. Kopito

  • Article |

    Mutations in the gene encoding DJ-1 are associated with early-onset familial forms of Parkinson’s disease, and several different molecular functions have been attributed to this protein. Moscovitz et al.show that DJ-1 physically binds the 20S proteasome and inhibits its degradation activity.

    • Oren Moscovitz
    • , Gili Ben-Nissan
    •  & Michal Sharon

  • Article
    | Open Access

    Aberrant hippocampal neurogenesis often occurs after acute seizures that produce epilepsy and cognitive impairment but the role of neurogenesis in the development of epilepsy is unclear. Here the authors suppress adult neurogenesis in mice preceding seizures and show that it reduces subsequent chronic seizure frequency and epilepsy-associated cognitive decline.

    • Kyung-Ok Cho
    • , Zane R. Lybrand
    •  & Jenny Hsieh

  • Article |

    Applications of human pluripotent stem cells (hPSCs) for disease modelling or cell therapy are hindered by low efficiency and heterogeneity of target cell types differentiated from hPSCs, such as motor neurons (MNs). Here the authors develop a method to derive highly pure motor neuron progenitor populations from human embryonic and induced pluripotent stem cells that yield functional MNs.

    • Zhong-Wei Du
    • , Hong Chen
    •  & Su-Chun Zhang

  • Article
    | Open Access

    Membrane depolarization during increased neuronal activity as seen during epilepsy has been suggested to easily reverse neuronal GABA transporters. Here the authors use modelling and experimental data and challenge this view by showing that synaptic GABA release during excessive neuronal firing averts reversal of GABA uptake.

    • Leonid Savtchenko
    • , Maria Megalogeni
    •  & Ivan Pavlov

  • Article
    | Open Access

    The targeting of inflammation has emerged as a promising therapeutic strategy for cerebral ischaemia. Here the authors show that TIM-3, a member of the T-cell immunoglobulin and mucin domain protein family, is upregulated in glial cells and plays a role in inflammation-associated brain injury under hypoxic conditions.

    • Han Seok Koh
    • , Chi Young Chang
    •  & Eun Jung Park

  • Article
    | Open Access

    Autism genes converge in midfetal cortical co-expression networks, and chromatin regulators such as CHD8 are increasingly associated with autism spectrum disorder (ASD). Here the authors map CHD8 targets in developing brain, and find that CHD8 directly regulates other ASD risk genes during human neurodevelopment.

    • Justin Cotney
    • , Rebecca A. Muhle
    •  & James P. Noonan

  • Article |

    In Alzheimer’s disease (AD), β-amyloid plaques are tightly enveloped by microglia but the significance of this phenomenon is unknown. Here the authors used confocal and in vivotwo-photon imaging in AD mouse models and revealed that microglia constitute a barrier that seems to prevent the formation of neurotoxic hotspots of protofibrillar β-amyloid.

    • Carlo Condello
    • , Peng Yuan
    •  & Jaime Grutzendler

  • Article
    | Open Access

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

    • Ching-Yu Cheng
    • , Kenji Yamashiro
    •  & Chiea Chuen Khor

  • Article |

    Dominant mutations in the RNA-binding protein FUS/TLS cause amyotrophic lateral sclerosis (ALS), an adult-onset motor neuron degenerative disease. Here, the authors show that ALS-causative FUS/TLS mutations directly bind the SMN and U1-snRNP complexes, producing both loss and gain of function effects on RNA processing.

    • Shuying Sun
    • , Shuo-Chien Ling
    •  & Don W. Cleveland

  • Article |

    Neurological disorders such as temporal lobe epilepsy (TLE) are known to be regulated by gene networks. In this study, the authors describe a genome-wide approach that uses samples of hippocampal tissue from patients with TLE, to identify the gene Sestrin 3 (SESN3) as a positive regulator of the disease.

    • Michael R. Johnson
    • , Jacques Behmoaras
    •  & Enrico Petretto

  • Article
    | Open Access

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects spinal cord motor neurons. Here the authors use induced pluripotent stem cell-derived motor neurons obtained from patients with ALS-linked mutations, and find functional deficits resulting from a progressive decrease in voltage-activated Na+ and K+currents that occur in the absence of cell death.

    • Anna-Claire Devlin
    • , Karen Burr
    •  & Gareth B. Miles

  • Article |

    The nuclear protein TDP-43 is implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Here, Cohen et al. discover lysine acetylation as a modification that regulates TDP-43 function, providing a mechanism that could be implicated in the pathogenesis of TDP-43 proteinopathies.

    • Todd J. Cohen
    • , Andrew W. Hwang
    •  & Virginia M. Y. Lee

  • Article |

    Small molecules that inhibit α-synuclein misfolding may have potential in the treatment of Parkinson’s disease. Fonseca-Ornelas et al.show that several of these molecules fail to block misfolding in the presence of membrane vesicles, and reveal how phtalocyanine tetrasulfonate, in contrast, overcomes this effect.

    • Luis Fonseca-Ornelas
    • , Sybille E. Eisbach
    •  & Markus Zweckstetter

  • Article
    | Open Access

    In the adult brain, the neurotrophic factor basic fibroblast growth factor (bFGF) is predominantly secreted by astrocytes. Here the authors use optogenetics to activate astrocytes, leading to release of bFGF, inducing enhanced dopaminergic differentiation of neural progenitors and promoting brain repair in a mouse Parkinson’s disease model.

    • Fan Yang
    • , Yunhui Liu
    •  & Liping Wang

  • Review Article |

    Proteins are subject to continuous and complex quality-control mechanisms, which ensure integrity of the proteome. Vilchez et al.review how a demise in these processes, collectively referred to as proteostasis, is linked to organismal ageing and the development of age-associated diseases.

    • David Vilchez
    • , Isabel Saez
    •  & Andrew Dillin

  • Article
    | Open Access

    Sphingosine is abnormally accumulated in Niemann–Pick type C disease (NP–C), but the causes of this accumulation have not been fully characterized. Here the authors show that sphingosine kinase activity is reduced in NP–C patient fibroblasts and NP–C mouse neurons due to defective vascular endothelial growth factor levels, suggesting therapeutic avenues.

    • Hyun Lee
    • , Jong Kil Lee
    •  & Hee Kyung Jin

  • Article |

    Astrocytic network alterations are seen in Alzheimer’s disease (AD) but the underlying mechanisms have remained undefined. Here the authors use in vivomulitphoton microscopy to monitor spontaneous network activity of astrocytes in a mouse model of AD, and find that astroglial hyperactivity was largely mediated by activation of the purinergic receptor P2Y1.

    • Andrea Delekate
    • , Martina Füchtemeier
    •  & Gabor C. Petzold

  • Article
    | Open Access

    Mitochondrial dysfunction has been associated with Parkinson’s disease but effective therapies targeting this pathway are yet to be developed. Here the authors show that inhibition of the mitochondrial fission protein Drp-1 using genetic or small-molecule approaches in mouse models of the disease, leads to improvements in the pathology.

    • Phillip M. Rappold
    • , Mei Cui
    •  & Kim Tieu

  • Article |

    Autism spectrum disorders (ASD) are characterized by social impairments, communication deficits and repetitive stereotyped behaviours. Here, the authors show that de novo missense mutations, but not inherited missense mutations, in TBR1disrupt the protein function and contribute to ASD aetiology.

    • Pelagia Deriziotis
    • , Brian J. O’Roak
    •  & Simon E. Fisher

  • Article |

    1H magnetic resonance can detect endogenous metabolites at physiological concentrations but its application in animal models is challenged by low sensitivity. Here the authors focus ultrahigh magnetic fields on metabolites whose spectral signatures are selectively excited, and achieve microarchitectural insight of rat brains after a stroke.

    • Noam Shemesh
    • , Jens T. Rosenberg
    •  & Lucio Frydman

  • Article |

    White matter in the human brain is known to change its properties during an individual's lifespan. Here, Yeatman et al. use quantitative imaging measurements of the living human brain to model changes in white mater structure based on tissue development and decline between the ages of 7–85 years.

    • Jason D. Yeatman
    • , Brian A. Wandell
    •  & Aviv A. Mezer

  • Article |

    Transmission of alpha-synuclein aggregates between neurons has been observed in animal models of Parkinson’s disease, however, the mechanism of transmission remains unclear. Bae et al. report that a cycle of uptake, co-aggregation and exocytosis is enhanced by loss of glucocerebrosidase activity.

    • Eun-Jin Bae
    • , Na-Young Yang
    •  & Seung-Jae Lee

  • Article |

    Impaired neuronal connectivity is implicated in autism spectrum disorder (ASD). In this study, the authors perform time-lapse imaging of brain neurons from different mouse models of ASD and provide evidence for enhanced turnover of excitatory synapses as a commonly occurring mechanism in ASD.

    • Masaaki Isshiki
    • , Shinji Tanaka
    •  & Shigeo Okabe

  • Article |

    As well as substantial changes in mood, geriatric depression is also characterized by executive dysfunction (ED). Morimoto et al.show that some sufferers of geriatric depression do not respond to conventional drugs, and that ED in these patients can be alleviated with computerized cognitive remediation therapy.

    • Sarah Shizuko Morimoto
    • , Bruce E. Wexler
    •  & George S. Alexopoulos

  • Article
    | Open Access

    Tuberous sclerosis complex (TSC) is a rare genetic condition characterized by epileptic seizures that start in infancy. Here, the authors show that these seizures are modulated by GluN2C-containing NMDA receptors in the cortex of a mouse model of TSC, and that suppressing their activity attenuates seizures.

    • N. Lozovaya
    • , S. Gataullina
    •  & N. Burnashev

  • Article
    | Open Access

    Compound 8-1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6(1H,3H,5H)-trione was previously reported to be a selective inhibitor of the CaV1.3 calcium channel. Now, Huang et al. demonstrate that selectivity towards CaV1.3 relative to CaV1.2 is dependent on the type of β-subunit and CaV1.3 splice variant assayed.

    • Hua Huang
    • , Cheng Yang Ng
    •  & Tuck Wah Soong

  • Article |

    Abnormal accumulation of the RNA-binding protein FUS and mutations within the FUS gene have been found in association with amyotrophic lateral sclerosis (ALS). Here, Dini Modigliani et al.uncover a FUS regulatory circuit that implicates the microRNAs miR-141 and miR-200a in a feedback loop disrupted by an ALS-associated mutation.

    • Stefano Dini Modigliani
    • , Mariangela Morlando
    •  & Irene Bozzoni

  • Article |

    α-synuclein is a protein whose aberrant aggregation is associated with Parkinson’s disease. Here, Fusco et al.characterize α-synuclein bound to lipid membranes using a combination of solution and solid-state NMR spectroscopy and provide insights into the molecular processes associated with the aggregation of this protein.

    • Giuliana Fusco
    • , Alfonso De Simone
    •  & Gianluigi Veglia

  • Article
    | Open Access

    Focal epilepsy is difficult to treat with currently available drugs or surgical approaches. Kätzel et al.express mutant inhibitory receptors in the brains of rats with focal epilepsy and selectively activate these receptors by an exogenous compound, which results in region- and time-specific suppression of focal seizures

    • Dennis Kätzel
    • , Elizabeth Nicholson
    •  & Dimitri M. Kullmann

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