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Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours
Synaptic plasticity in the nucleus accumbens is implicated in stress and addiction. Sim et al. study mice deficient in dopamine D2 receptors, and find an increase in anxiety behaviour and reduced addictive behaviour in response to stress, both of which are associated with changes in nucleus accumbens activity.
- Hye-ri Sim
- , Tae-Yong Choi
- & Ja-Hyun Baik
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Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia
Parkinson’s disease is associated with the accumulation of abnormal aggregates of α-synuclein and microglial neuroinflammation. Kim et al. show that α-synuclein oliogomers released by neurons activate microglia by stimulating Toll-like receptor 2 signalling in these cells.
- Changyoun Kim
- , Dong-Hwan Ho
- & Seung-Jae Lee
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Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex
Expansion of CAG repeats in messenger RNAs is a common feature of various neurodegenerative disorders, including Huntington’s disease. Krauß et al.show that messenger RNAs with expanded CAG repeats bind to a protein complex that regulates translation and promotes overproduction of such aberrant proteins.
- Sybille Krauß
- , Nadine Griesche
- & Susann Schweiger
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Holographic optogenetic stimulation of patterned neuronal activity for vision restoration
Photo-stimulation can be used to control neuronal circuits, but current strategies lack optimal precision and resolution. Reutsky-Gefen et al. demonstrate a potential approach for vision restoration via holographically patterned, optogenetic stimulation of retinal ganglion cells, with temporal precision.
- Inna Reutsky-Gefen
- , Lior Golan
- & Shy Shoham
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Smoking exacerbates amyloid pathology in a mouse model of Alzheimer’s disease
A link between smoking and the incidence of Alzheimer’s disease has been implicated in humans. In this study, transgenic mouse models of Alzheimer’s disease exposed to cigarette smoke display increased disease abnormalities in the brain, such as amyloidogenesis, neuroinflammation and tau phosphorylation.
- Ines Moreno-Gonzalez
- , Lisbell D. Estrada
- & Claudio Soto
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Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival
Botulinum toxins can cause substantial neurodegeneration. Peng et al. study cultured rat hippocampal neurons and find that botulinum toxin-induced cytotoxicity occurs only when there is effective cleavage of the SNARE proteins, syntaxin 1 or SNAP-25, by type C and type E botulinum toxins.
- Lisheng Peng
- , Huisheng Liu
- & Min Dong
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Perceiving invisible light through a somatosensory cortical prosthesis
Primary sensory areas of newborn mammals typically display input-dependent plasticity. Thomson and colleagues use a sensory prosthetic device in rats to show that adult rats can discriminate different infrared light signals, when the signals are routed to somatosensory cortex by electrical microstimulation.
- Eric E. Thomson
- , Rafael Carra
- & Miguel A.L. Nicolelis
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| Open AccessA point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration
Semaphorin 4A is implicated in photoreceptor survival. Nojima and colleagues generate transgenic mice with different mutations in the Sema4A gene and find that point mutation of F350 causes severe degeneration in photoreceptor cells, which can be rescued by virus-mediated gene therapy.
- Satoshi Nojima
- , Toshihiko Toyofuku
- & Atsushi Kumanogoh
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| Open AccessOn-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy
Temporal lobe epilepsy in adults does not always respond to treatment. Krook-Magnuson and colleagues use optogenetics to inhibit and activate excitatory and inhibitory neurons, respectively, in a mouse model of temporal lobe epilepsy, and find that they can stop seizures on a moment-to-moment basis.
- Esther Krook-Magnuson
- , Caren Armstrong
- & Ivan Soltesz
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A safe lithium mimetic for bipolar disorder
Lithium is commonly used to treat bipolar disorder, but it exerts side effects at doses close to the therapeutic range. Singh and colleagues screen a collection of clinical compounds and find that ebselen induces lithium-like effects on mouse models of bipolar disorder by inhibiting inositol monophosphatase.
- Nisha Singh
- , Amy C. Halliday
- & Grant C. Churchill
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Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated Aβ toxicity in Drosophila
PAR-1 inDrosophilahas been identified as a key physiological tau kinase. Lee and colleagues perform genetic screens for regulators of PAR-1 and find that it is targeted for ubiquitination and degradation by the ubiquitin ligase complex SCF(Slimb), and that this pathway modulates synaptic morphology.
- Seongsoo Lee
- , Ji-Wu Wang
- & Bingwei Lu
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| Open AccessRapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex
Tuberous sclerosis complex is an autosomal dominant cognitive disorder caused by mutations affecting TSCgenes. Sato and colleagues examine tuberous sclerosis complex mutant mice and find that the behavioural and anatomical abnormalities can be reversed by inhibiting rapamycin-sensitive signalling pathways, even in adulthood.
- Atsushi Sato
- , Shinya Kasai
- & Masashi Mizuguchi
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A role for calpain-dependent cleavage of TDP-43 in amyotrophic lateral sclerosis pathology
The mislocalization and downregulation of the proteins TDP-43 and ADAR2, respectively, are implicated in amyotrophic lateral sclerosis pathology. Yamashita et al. find that downregulation of ADAR2 results in calcium-permeable AMPA receptor-mediated calpain activation and subsequent aberrant cleavage of TDP-43.
- Takenari Yamashita
- , Takuto Hideyama
- & Shin Kwak
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Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel
Mutations of the NaV1.7 voltage-gated sodium channel are implicated in abnormal pain signal transduction. Yang and colleagues perform structural modeling, mutant cycle analysis and electrophysiology on specific mutants and find that they can accurately predict their response profiles to channel blockers.
- Yang Yang
- , Sulayman D. Dib-Hajj
- & Stephen G. Waxman
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| Open AccessStructural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons
Mutations in human angiogenin are implicated in the progression of amyotrophic lateral sclerosis. Thiyagarajan and colleagues show that structural differences between angiogenin variants affect neuronal survival, and the ability to induce stress granules in neuronal cell lines.
- Nethaji Thiyagarajan
- , Ross Ferguson
- & K. Ravi Acharya
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| Open AccessEvidence of an inhibitory restraint of seizure activity in humans
Seizure activity in the brain is characterized by the recruitment of cortical neuronal activity. Schevon and colleagues study seizure activity in human subjects and find that the recruitment of neurons is hypersynchronous and that there is an intrinsic restraint on the propagation of this activity.
- Catherine A. Schevon
- , Shennan A. Weiss
- & Andrew J. Trevelyan
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Structured neuronal encoding and decoding of human speech features
Speech is encoded by the firing patterns of speech-controlling neurons in different regions of the brain, which Tankus and colleagues analyse in this study. They find highly specific encoding of vowels in medial–frontal neurons and nonspecific tuning in superior temporal gyrus neurons.
- Ariel Tankus
- , Itzhak Fried
- & Shy Shoham
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| Open AccessTargeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury
Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.
- Matthew Campbell
- , Finnian Hanrahan
- & Peter Humphries
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Soluble amyloid precursor protein-α modulates β-secretase activity and amyloid-β generation
The loss of neurotrophic factors is responsible for key neurodegenerative processes in Alzheimer's disease. In this study, Obregon and colleagues treat amyloidogenic cells with the neurotrophin soluble amyloid precursor protein-α and find that it halts amyloidogenesis by interacting with the β-secretase BACE1.
- Demian Obregon
- , Huayan Hou
- & Jun Tan
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| Open AccessStaged decline of neuronal function in vivo in an animal model of Alzheimer's disease
The amyloid-β-peptide is pivotal to the pathology of Alzheimer's disease, but its mechanism of action remains uncertain. This study utilizesin vivotwo-photon calcium imaging to investigate the effects of this peptide on single cortical neurons of the visual cortex in a mouse model of Alzheimer's disease.
- Christine Grienberger
- , Nathalie L. Rochefort
- & Arthur Konnerth
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| Open AccessSUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair
Tyrosyl DNA phosphodiesterase 1 (TDP1) repairs DNA breaks and is mutated in the disease Spinocerebellar Ataxia with Axonal Neuropathy. Here TDP1 is shown to be post-translationally modified by sumoylation of lysine 111, and cells carrying a mutation at this residue are inefficient at single-strand DNA break repair.
- Jessica J.R. Hudson
- , Shih-Chieh Chiang
- & Sherif F. El-Khamisy
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| Open Accessγ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor
Glutathione's key role as a modulator of reactive oxygen species levels has recently been challenged. Quintana-Cabreraet al. now provide in vivoevidence supporting an antioxidant and neuroprotective function for γ-glutamylcysteine, which replaces glutathione by acting as glutathione peroxidase-1 cofactor.
- Ruben Quintana-Cabrera
- , Seila Fernandez-Fernandez
- & Juan P. Bolaños
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Tactile stimulation lowers stress in fish
The health benefits of massage therapy, like the reduction of stress, have so far only been shown in humans. This study uses modelling to demonstrate that, while visiting cleaner fish to have ectoparasites removed, the physical stimulation also acts to reduce stress in the coral reef fish,Ctenochaetus striatus.
- Marta C. Soares
- , Rui F. Oliveira
- & Redouan Bshary
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| Open AccessParkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus
Pluripotent stem cells can be generated from the somatic cells of humans and are a useful model to study disease. Here, pluripotent stem cells are made from a patient with familial Parkinson's disease, and the resulting neurons exhibit elevated levels of α-synuclein, recapitulating the molecular features of the patient's disease.
- Michael J. Devine
- , Mina Ryten
- & Tilo Kunath
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| Open AccessGlia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration
The central nervous system contains glial cells, which have been shown to have an important role in neuronal survival. Haradaet al. use transgenic mouse models to show that TrkB, a receptor for the growth factor brain-derived neurotrophic factor, is required for retinal Müller glial cells to provide neuroprotection and regeneration.
- Chikako Harada
- , Xiaoli Guo
- & Takayuki Harada
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| Open AccessSubstrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site
γ-Secretase modulators have promise in the treatment of Alzheimer's disease, but their molecular target is uncertain. Here, fluorescence resonance energy transfer is used to determine that the γ-secretase allosteric site is within the γ-secretase complex and that substrate docking is required for modulators to access the site.
- Kengo Uemura
- , Katherine C. Farner
- & Oksana Berezovska
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| Open AccessA β-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain
Little is known about β-synuclein mutations in neurological disease. In this article, the authors demonstrate that mice with a mutation in β-synuclein show progressive neurodegenerative disease and suggest that this mutation can enhance the brain defects caused by α-synuclein mutations in mice.
- Masayo Fujita
- , Shuei Sugama
- & Makoto Hashimoto
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Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A
The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.
- Yasushi Ogawa
- , Yosuke Nonaka
- & Masatoshi Hagiwara
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