Diseases of the nervous system articles within Nature Communications

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  • Article
    | Open Access

    Mutations in spermine synthase lead to Snyder-Robinson syndrome, a form of intellectual disability syndrome. Here the authors develop a Drosophila model of this disease, and show that lysosomal dysfunction and oxidative stress contribute to the morphological phenotype in these flies, as well as to cellular deficits in cells derived from patients.

    • Chong Li
    • , Jennifer M. Brazill
    •  & R. Grace Zhai

  • Article
    | Open Access

    Abnormal levels of Aβ42 in the cerebrospinal fluid occur prior to a positive amyloid PET scan in the brain of individuals with Alzheimer’s disease and here the authors use this temporal pattern to identify individuals with very early stage AD. They show that Aβ fibrils start to accumulate in some of the regions of the default mode network and affect brain connectivity before neurodegeneration occurs.

    • Sebastian Palmqvist
    • , Michael Schöll
    •  & Oskar Hansson

  • Article
    | Open Access

    Accumulating evidence suggests that disruption of autophagy is associated with neurodegeneration. Here the authors show that Plekhg5 acts as a GEF for Rab26, a small GTPase that promotes the autophagy of synaptic vesicles in neurons; mice lacking Plekgh5 develop late-onset motoneuron degeneration.

    • Patrick Lüningschrör
    • , Beyenech Binotti
    •  & Michael Sendtner

  • Article
    | Open Access

    Existing methods to improve motor function after stroke include non-specific neuromodulatory approaches. Here the authors use an automated method of analysis of reaching behaviour in rodents to show that optogenetic stimulation of intact corticospinal tract fibres leads to restoration of prior motor functions, rather than compensatory acquisition of new movements.

    • A. S. Wahl
    • , U. Büchler
    •  & M. E. Schwab

  • Article
    | Open Access

    Astrocytes can have protective or detrimental effects on neurons during injury, but the molecular mechanisms that determine these different states are unresolved. Here the authors identify a pathway via neuronal EphB1 that induces neuroprotective signalling in astrocytes through ephrin-B1 mediated STAT3 activation, which is impaired in models of amyotrophic lateral sclerosis.

    • Giulia E. Tyzack
    • , Claire E. Hall
    •  & András Lakatos

  • Article
    | Open Access

    Functional consequence of transient delay in neuronal migration is unclear. This study shows that Wnt/C-Kit signaling regulates radial migration in rat somatosensory cortex, and that transient delay of L2/3 neuronal migration leads to interhemispheric connectivity alteration and abnormal social behavior.

    • Riccardo Bocchi
    • , Kristof Egervari
    •  & Jozsef Z. Kiss

  • Article
    | Open Access

    Dysfunction of mGluR5 has been implicated in Fragile X syndrome. Here, using a single-molecule tracking technique, the authors found an increased lateral mobility of mGluR5 at the synaptic site in Fmr1 KO hippocampal neurons, leading to abnormal NMDAR-mediated synaptic plasticity and cognitive deficits.

    • Elisabetta Aloisi
    • , Katy Le Corf
    •  & Andreas Frick

  • Article
    | Open Access

    Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI.

    • Onder Albayram
    • , Asami Kondo
    •  & Xiao Zhen Zhou

  • Article
    | Open Access

    Amyotrophic lateral sclerosis (ALS) leads to selective loss of motor neurons. Using motor neurons derived from induced pluripotent stem cells from patients with ALS and FUS mutations, the authors demonstrate that axonal transport deficits that are observed in these cells can be rescued by HDAC6 inhibition.

    • Wenting Guo
    • , Maximilian Naujock
    •  & Ludo Van Den Bosch

  • Article
    | Open Access

    Seeding of amyloid beta from one brain region to another is thought to contribute to the progression of Alzheimer’s disease, although to date most studies have depended on inoculation of animals with exogenous amyloid. Here the authors describe a genetic seed and target system in Drosophila which may be useful for the mechanistic study of seeding of amyloid in vivo.

    • Ramona F. Sowade
    •  & Thomas R. Jahn

  • Article
    | Open Access

    Excitotoxicity contributes to neuronal injury following stroke. Here the authors show that tau promotes excitotoxicity by a post-synaptic mechanism, involving site-specific control of ERK activation, in a mouse model of stroke.

    • Mian Bi
    • , Amadeus Gladbach
    •  & Lars M. Ittner

  • Article
    | Open Access

    Focal cortical seizures result from local and widespread propagation of excitatory activity. Here the authors employ widefield calcium imaging in mouse visual areas to demonstrate that these seizures start as local synchronous activation and then propagate along the connectivity that underlies normal sensory processing.

    • L. Federico Rossi
    • , Robert C. Wykes
    •  & Matteo Carandini

  • Article
    | Open Access

    Intra-hippocampal circuits are essential for associating a background context with behaviorally salient stimuli and involve cholinergic modulation at SST+ interneurons. Here the authors show that the salience of the background context memory is modulated through muscarinic activation of NPY+ hilar perforant path associated interneurons and NPY signaling in the dentate gyrus.

    • Syed Ahsan Raza
    • , Anne Albrecht
    •  & Oliver Stork

  • Article
    | Open Access

    The RNA for ALS- and frontotemporal dementia-associated C9ORF72 gene is exported from nucleus via an unknown mechanism. This study shows that reduction of nuclear export adaptor SRSF1 can alleviate neuronal cell death and nuclear export of C9ORF72 inDrosophilaand patient-derived induced motor neurons.

    • Guillaume M. Hautbergue
    • , Lydia M. Castelli
    •  & Pamela J. Shaw

  • Article
    | Open Access

    TDP-43 aggregation is observed in amyotrophic lateral sclerosis. Here the authors combine X-ray crystallography, nuclear magnetic resonance and electron microscopy studies and show that physiological oligomerization of TDP-43 is mediated through its N-terminal domain, which forms functional and dynamic oligomers antagonizing pathologic aggregation.

    • Tariq Afroz
    • , Eva-Maria Hock
    •  & Magdalini Polymenidou

  • Article
    | Open Access

    Astrocytic phagocytosis has been shown to play a role in synaptic pruning during development, but whether adult astrocytes possess phagocytic ability is unclear. Here the authors show that following brain ischemia, reactive astrocytes become phagocytic and engulf debris via the ABCA1 pathway.

    • Yosuke M. Morizawa
    • , Yuri Hirayama
    •  & Schuichi Koizumi

  • Article
    | Open Access

    Mutations inCHCHD10 have been recently associated with frontotemporal dementia and amyotrophic lateral sclerosis. Here the authors study the functions of endogenous CHCHD10 in Caenorhabditis elegans, primary neurons, and mouse, and show that it normally protects mitochondria and synaptic integrity, and retains TDP-43 in the nucleus.

    • Jung-A. A. Woo
    • , Tian Liu
    •  & David E. Kang

  • Article
    | Open Access

    Features of major depressive disorder including lack of motivation, sleep disruption and cognitive deficit have been modelled in rodents. Here, the authors develop a new method to elicit a depression-like state inDrosophila, and uncover separable roles for different serotonin receptors in depression-like behaviour.

    • Ariane-Saskia Ries
    • , Tim Hermanns
    •  & Roland Strauss

  • Article
    | Open Access

    Mutations in the granulin gene are associated with frontotemporal lobe dementia (FTLD) and a lysosomal storage disease. The authors show that reduced progranulin levels leads to impaired neuronal uptake and lysosomal delivery of prosaposin, and that decreased prosaposin expression in mice leads to FTLD-like behaviour.

    • Xiaolai Zhou
    • , Lirong Sun
    •  & Fenghua Hu

  • Article
    | Open Access

    Mislocalisation of tau occurs in several neurodegenerative diseases and is thought to contribute to synaptic function. The authors show that presynaptically, tau binds to synaptic vesicles via the N-terminus which contributes to synaptic dysfunction.

    • Lujia Zhou
    • , Joseph McInnes
    •  & Patrik Verstreken

  • Article
    | Open Access

    Angelman syndrome (AS) is characterized by developmental delay and intellectual disability, but the underlying pathophysiology is not well understood. Here the authors use induced pluripotent stem cell-derived neurons from AS patients and find impaired maturation of resting membrane potential and action potential firing, and defects in synaptic activity associated with the disease.

    • James J. Fink
    • , Tiwanna M. Robinson
    •  & Eric S. Levine

  • Article
    | Open Access

    The authors record both local and long-range neural activity during human epileptic seizures to study the underlying multi-scale dynamics. They find that coupling of activity across spatial scales increases during seizures through propagating waves that are fit by a model that combines neural activity and potassium concentration dynamics.

    • L-E Martinet
    • , G. Fiddyment
    •  & M. A. Kramer

  • Article
    | Open Access

    Dystonia is thought to be driven by impairments in cerebellar signalling. The authors use a mouse genetic approach to silence excitatory transmission in the inferior olive to cerebellum pathway, resulting in dystonia-like signs in the animals which can be alleviated using DBS stimulation of the pathway.

    • Joshua J. White
    •  & Roy V. Sillitoe

  • Article
    | Open Access

    Dopaminergic dysfunction occurs in Alzheimer’s disease (AD). The authors show that in a mouse model of AD, loss of dopaminergic neurons in the ventral tegmental area, but not the substantia nigra, occurs at early pre-plaque stages, and may contribute to impaired cognition and reward processing.

    • Annalisa Nobili
    • , Emanuele Claudio Latagliata
    •  & Marcello D’Amelio

  • Article
    | Open Access

    Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

    • Russell L. McLaughlin
    • , Dick Schijven
    •  & Michael C. O’Donovan

  • Article
    | Open Access

    Glial scars are thought to provide a biochemical and mechanical barrier to neuronal regeneration post-injury, but the mechanical properties of the scars have not been studied in detail. Here the authors perform atomic force microscopy measurements of glial scars from the injured rat cortex and spinal cord, and find that brain tissue softens in response to the injury.

    • Emad Moeendarbary
    • , Isabell P. Weber
    •  & Kristian Franze

  • Article
    | Open Access

    Mutations in the chromatin modifier Chd7 have been associated with CHARGE syndrome and other developmental disorders. Here the authors show that Chd7 is required for the activation of genes essential for cerebellar granule cell differentiation, and that disrupting Chd7 leads to cerebellar hypoplasia in mice.

    • Weijun Feng
    • , Daisuke Kawauchi
    •  & Hai-Kun Liu

  • Article
    | Open Access

    Studying the physiological confirmation of amyloid β (Aβ) and amyloid precursor protein (APP) often uses techniques that could disrupt their conformation. Here, the authors use non-destructive microscopy approaches to study the confirmation of Aβ and APP in mouse models of Alzheimer’s disease.

    • O. Klementieva
    • , K. Willén
    •  & G. K. Gouras

  • Article
    | Open Access

    Fragile X syndrome (FXS) is a leading cause of autism and neurons lacking FMRP show aberrant mRNA translation and intracellular signalling. Here, the authors show that neurons from Fmr1 knockout mice have increased levels of ADCY1 protein, producing abnormal ERK1/2 signalling, dysregulated protein synthesis and behavioural symptoms associated with FXS.

    • Ferzin Sethna
    • , Wei Feng
    •  & Hongbing Wang

  • Article
    | Open Access

    Pain is affected by cerebral processes in addition to afferent nociceptive input. Here the authors develop an fMRI-based signature that predicts pain independent of the intensity of nociceptive signals and mediates the pain-modulating effects of several cognitive interventions.

    • Choong-Wan Woo
    • , Liane Schmidt
    •  & Tor D. Wager

  • Article
    | Open Access

    Huntington’s disease (HD) is caused by misfolding of mutant Htt protein. The authors find that in HD models, the decreased expression of heat shock transcription factor 1 that usually protects against protein misfolding, is in part caused by elevated CK2α’ kinase and Fbxw7 E3 ligase expression.

    • Rocio Gomez-Pastor
    • , Eileen T. Burchfiel
    •  & Dennis J. Thiele

  • Article
    | Open Access

    Schizophrenia is a mental disorder characterized by hallucinations and delusions. Here the authors report a novel probabilistic inference task in which compared to healthy subjects, schizophrenia patients show greater degree of circular inference that matches the severity of their clinical symptoms.

    • Renaud Jardri
    • , Sandrine Duverne
    •  & Sophie Denève

  • Article
    | Open Access

    Cholesterol is important for axonal myelination during development. Here the authors show that cholesterol levels are reduced in a cuprizone mouse model of multiple sclerosis and that dietary cholesterol supplementation enhances remyelination and recovery.

    • Stefan A. Berghoff
    • , Nina Gerndt
    •  & Gesine Saher

  • Article
    | Open Access

    PrPC protein plays a key role in prion transmission across species. Here, the authors compare transmission of a representative scrapie isolate to transgenic mice expressing variable levels of the same Prnp allele as the donor sheep, and find divergent strain propagation regulated by PrPCgene dosage.

    • Annick Le Dur
    • , Thanh Lan Laï
    •  & Hubert Laude

  • Article
    | Open Access

    Glut1-deficiency syndrome is a severe neurodevelopmental disorder characterized by low brain glucose and epileptic seizures. Tanget al. show that in model mice, low Glut1 leads to defects of the brain vasculature, and that AAV9-based gene therapy at pre- or early-symptomatic stages prevents the defects and mitigates disease.

    • Maoxue Tang
    • , Guangping Gao
    •  & Umrao R. Monani

  • Article
    | Open Access

    Rett syndrome is associated with impaired synaptic connectivity beginning in early development. Here the authors show in female mice heterozygous forMecp2, a model of Rett syndrome, that during adulthood, auditory cortex plasticity associated with a learned maternal behaviour is also impaired.

    • Keerthi Krishnan
    • , Billy Y. B. Lau
    •  & Stephen D. Shea

  • Article
    | Open Access

    Sex differences in reward processing are at present poorly understood. Calipari and Juarezet al. report oestrous cycle-dependent fluctuations in firing of VTA dopamine neurons that drive alterations in DAT function expressed in terminals in the NAc. These differences underlie enhanced cocaine reward processing during oestrus.

    • Erin S. Calipari
    • , Barbara Juarez
    •  & Eric J Nestler

  • Article
    | Open Access

    Longevity of antibody responses has been attributed to persistence of plasma cells in mice. Here the authors provide human data in support of this model by immunoglobulin sequencing bone marrow sections from two human donors over 6.5 years to show temporal stability of plasma cell clonotypes, but not other B cells.

    • Gabriel C. Wu
    • , Nai-Kong V. Cheung
    •  & Gregory C. Ippolito

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