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https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#1
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28599322/monoamine-oxidase-a-upregulated-by-chronic-intermittent-hypoxia-activates-indoleamine-2-3-dioxygenase-and-neurodegeneration
#2
Chun-Sing Lam, Jing-Jie Li, George Lim Tipoe, Moussa B H Youdim, Man-Lung Fung
Co-morbid depression is prevalent in patients with obstructive sleep apnea. Here we report that monoamine oxidase A (MAO-A) plays pathogenic roles in the comorbidity. We found that chronic intermittent hypoxia significantly increased the MAO-A expression in the rat hippocampus and markedly decreased the dendritic length and spine density in the pyramidal neurons with less pre- and post-synaptic proteins. The MAO-A upregulation resulted in increased 5-hydroxyindoleacetic acid/serotonin ratio, oxidative stress, leading to NF-κB activation, inflammation and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28553222/dynamic-arc-sumoylation-and-selective-interaction-with-f-actin-binding-protein-drebrin-a-in-ltp-consolidation-in-vivo
#3
Rajeevkumar R Nair, Sudarshan Patil, Adrian Tiron, Tambudzai Kanhema, Debabrata Panja, Lars Schiro, Kamil Parobczak, Grzegorz Wilczynski, Clive R Bramham
Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as a master regulator of long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. Post-translation modification by small ubiquitin-like modifier (SUMO) proteins has emerged as a major mechanism for regulating protein-protein interactions and function. We first show in cell lines that ectopically expressed Arc undergoes mono-SUMOylation. The covalent addition of a single SUMO1 protein was confirmed by in vitro SUMOylation of immunoprecipitated Arc...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28545543/inhibition-of-colony-stimulating-factor-1-receptor-early-in-disease-ameliorates-motor-deficits-in-sca1-mice
#4
Wenhui Qu, Andrea Johnson, Joo Hyun Kim, Abigail Lukowicz, Daniel Svedberg, Marija Cvetanovic
BACKGROUND: Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1...
May 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28539417/exposure-to-stressors-facilitates-long-term-synaptic-potentiation-in-the-lateral-habenula
#5
Hoyong Park, Jeehae Rhee, Kwanghoon Park, Jung-Soo Han, Roberto Malinow, ChiHye Chung
The lateral habenula (LHb) is a small part of the epithalamus that projects to monoamine centers in the brain. Previously, neurotransmission onto the LHb was shown to be abnormally potentiated in animal models of depression. However, synaptic plasticity in this brain area and the effect of stressor exposure on synaptic plasticity of the LHb have not been investigated. Thus, we explored whether the LHb undergoes dynamic changes in synaptic efficacy or not. First, we observed that a moderate long-term potentiation (LTP) occurs in a fraction of LHb neurons obtained from naïve Sprague Dawley rats...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28535798/using-kalirin-conditional-knockout-mice-to-distinguish-its-role-in-dopamine-receptor-mediated-behaviors
#6
Taylor P LaRese, Yan Yan, Betty A Eipper, Richard E Mains
BACKGROUND: Mice lacking Kalirin-7 (Kal7(KO)), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-D-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine...
May 23, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28512860/intrinsic-cellular-and-molecular-properties-of-in-vivo-hippocampal-synaptic-plasticity-are-altered-in-the-absence-of-key-synaptic-matrix-molecules
#7
Stephan Jansen, Christine Gottschling, Andreas Faissner, Denise Manahan-Vaughan
Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca(2+) -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-D-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C and tenascin-R (TG)...
May 17, 2017: Hippocampus
https://www.readbyqxmd.com/read/28473257/stress-and-corticosterone-alter-synaptic-plasticity-in-a-rat-model-of-parkinson-s-disease
#8
YongXin Hao, Aref Shabanpoor, Gerlinde A Metz
As a major influence on neuronal function and plasticity, chronic stress can affect the progression and symptoms of neurodegenerative conditions, such as Parkinson's disease (PD). Here we investigated the influence of unilateral dopamine depletion and stress on dopamine-related hallmarks of stress response and neuronal plasticity in a rat model of PD. Animals received either restraint stress or a combination of adrenalectomy and corticosterone (CORT) supplementation to clamp circulating glucocorticoid levels for three weeks prior to unilateral nigrostriatal dopamine depletion...
June 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28472657/structural-bases-of-desensitization-in-ampa-receptor-auxiliary-subunit-complexes
#9
Edward C Twomey, Maria V Yelshanskaya, Robert A Grassucci, Joachim Frank, Alexander I Sobolevsky
Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28469556/integrative-analysis-of-brain-region-specific-shank3-interactomes-for-understanding-the-heterogeneity-of-neuronal-pathophysiology-related-to-shank3-mutations
#10
Yeunkum Lee, Hyojin Kang, Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Won-Ki Kim, Kihoon Han
Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28463587/mild-traumatic-brain-injury-leads-to-decreased-inhibition-and-a-differential-response-of-calretinin-positive-interneurons-in-the-injured-cortex
#11
Mariana Brizuela, Catherine A Blizzard, Jyoti A Chuckowree, Kimberley A Pitman, Kaylene M Young, Tracey Dickson
It is clear that even mild forms of traumatic brain injury (TBI) can have lasting cognitive effects, however the specific cellular changes responsible for the functional deficits remain poorly understood. Previous studies suggest that not all neurons respond in the same way, and that changes to neuronal architecture may be subtype-specific. The current study aimed to characterize the response of interneurons to TBI. To model TBI in vitro, the neurites of primary cortical neurons were transected at 15 days in vitro...
May 2, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28442991/a-novel-long-non-coding-rna-durga-modulates-dendrite-density-and-expression-of-kalirin-in-zebrafish
#12
Mayuresh A Sarangdhar, Divya Chaubey, Abhishek Bhatt, Monisha Km, Manish Kumar, Shashi Ranjan, Beena Pillai
Kalirin, a key player in axonal development, nerve growth and synaptic re-modeling, is implicated in many pathological conditions like schizophrenia and autism-spectrum disorders. Alternative promoters and splicing lead to functionally distinct isoforms, but the post-transcriptional regulation of Kalirin has not been studied. Here, we report a novel non-coding RNA, which we name durga, arising from the first exon of kalirin a (kalrna) in the antisense orientation in zebrafish. The kalrna and durga transcripts are barely detectable during early development, but steadily increase by 24 hours post-fertilization (hpf) as the brain develops...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28439226/the-phosphodiesterase-10a-inhibitor-pf-2545920-enhances-hippocampal-excitability-and-seizure-activity-involving-the-upregulation-of-glua1-and-nr2a-in-post-synaptic-densities
#13
Yanke Zhang, Baobing Gao, Fangshuo Zheng, Shanshan Lu, Yun Li, Yan Xiong, Qin Yang, Yong Yang, Pengfei Fu, Fei Xiao, Xuefeng Wang
Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the strength of excitatory neural circuits and/or decrease inhibitory synaptic plasticity. Abnormally, synchronized synaptic transmission in the brain leads to seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently attracted attention as a potential therapy for neurological and psychiatric disorders. We hypothesized that PF-2545920 plays an important role in status epilepticus (SE) and investigated the underlying mechanisms...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28411102/zl006-protects-spinal-cord-neurons-against-ischemia-induced-oxidative-stress-through-ampk-pgc-1%C3%AE-sirt3-pathway
#14
Shu-Guang Liu, Yun-Mei Wang, Yan-Jun Zhang, Xi-Jing He, Tao Ma, Wei Song, Yu-Min Zhang
Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades, including activation of glutamate receptors and downstream signaling. Post-synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS) with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in the CNS. This molecular complex-mediated cytotoxicity has been implicated in brain ischemia, but its role in SCI has not been determined. The goal of the study was to investigate the potential protective effects of ZL006, a small-molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons...
April 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28397041/effects-of-nourishing-liver-and-kidney-acupuncture-therapy-on-expression-of-brain-derived-neurotrophic-factor-and-synaptophysin-after-cerebral-ischemia-reperfusion-in-rats
#15
Wen-Guang Xia, Chan-Juan Zheng, Xuan Zhang, Juan Wang
The aim of the present study was to investigate the effect of "nourishing liver and kidney" acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28384403/high-density-individually-addressable-nanowire-arrays-record-intracellular-activity-from-primary-rodent-and-human-stem-cell-derived-neurons
#16
Ren Liu, Renjie Chen, Ahmed T Elthakeb, Sang Heon Lee, Sandy Hinckley, Massoud L Khraiche, John Scott, Deborah Pre, Yoontae Hwang, Atsunori Tanaka, Yun Goo Ro, Albert K Matsushita, Xing Dai, Cesare Soci, Steven Biesmans, Anthony James, John Nogan, Katherine L Jungjohann, Douglas V Pete, Denise B Webb, Yimin Zou, Anne G Bang, Shadi A Dayeh
We report a new hybrid integration scheme that offers for the first time a nanowire-on-lead approach, which enables independent electrical addressability, is scalable, and has superior spatial resolution in vertical nanowire arrays. The fabrication of these nanowire arrays is demonstrated to be scalable down to submicrometer site-to-site spacing and can be combined with standard integrated circuit fabrication technologies. We utilize these arrays to perform electrophysiological recordings from mouse and rat primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons, which revealed high signal-to-noise ratios and sensitivity to subthreshold postsynaptic potentials (PSPs)...
April 10, 2017: Nano Letters
https://www.readbyqxmd.com/read/28379212/effects-of-epidural-compression-on-stellate-neurons-and-thalamocortical-afferent-fibers-in-the-rat-primary-somatosensory-cortex
#17
Tzu-Yin Yeh, Guo-Fang Tseng, Chi-Yu Tseng, Yung-Hsin Huang, Pei-Hsin Liu
A number of neurological disorders such as epidural hematoma can cause compression of cerebral cortex. We here tested the hypothesis that sustained compression of primary somatosensory cortex may affect stellate neurons and thalamocortical afferent (TCA) fibers. A rat model with barrel cortex subjected to bead epidural compression was used. Golgi-Cox staining analyses showed the shrinkage of dendritic arbors and the stripping of dendritic spines of stellate neurons for at least 3 months post-lesion. Anterograde tracing analyses exhibited a progressive decline of TCA fiber density in barrel field for 6 months post-lesion...
2017: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/28361374/spatial-gradients-in-the-size-of-inner-hair-cell-ribbons-emerge-before-the-onset-of-hearing-in-rats
#18
Radha Kalluri, Maya Monges-Hernandez
The size and locations of pre-synaptic ribbons and glutamate receptors within and around inner hair cells are correlated with auditory afferent response features such as the spontaneous discharge rate (SR), threshold, and dynamic range of sound intensity representation (the so-called SR-groups). To test if the development of these spatial gradients requires experience with sound intensity, we quantified the size and spatial distribution of synaptic ribbons from the inner hair cells of neonatal rats before and after the onset of hearing (from post-natal day (P) 3 to P33)...
June 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28355559/altered-synapse-stability-in-the-early-stages-of-tauopathy
#19
Johanna S Jackson, Jonathan Witton, James D Johnson, Zeshan Ahmed, Mark Ward, Andrew D Randall, Michael L Hutton, John T Isaac, Michael J O'Neill, Michael C Ashby
Synapse loss is a key feature of dementia, but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a mismatch in synapse turnover; postsynaptic spines turn over more rapidly, whereas presynaptic boutons are stabilized. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically driven neuronal activity in pre-degenerative stages of the disease...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28344334/the-kif1a-homolog-unc-104-is-important-for-spontaneous-release-postsynaptic-density-maturation-and-perisynaptic-scaffold-organization
#20
Yao V Zhang, Shabab B Hannan, Jeannine V Kern, Doychin T Stanchev, Baran Koç, Thomas R Jahn, Tobias M Rasse
The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104(bris), impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot...
March 27, 2017: Scientific Reports
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