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Chronic Intermittent Hypobaric Hypoxia Restores Hippocampus Function and Rescues Cognitive Impairments in Chronic Epileptic Rats via Wnt/β-catenin Signaling Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-22 Can Sun; Jian Fu; Zhenzhen Qu; Lijing Jia; Dongxiao Li; Junli Zhen; Weiping Wang
Epilepsy is a complex neurological disorder with frequent psychiatric, cognitive, and social comorbidities in addition to recurrent seizures. Cognitive impairment, one of the most common comorbidities, has severe adverse effects on quality of life. Chronic intermittent hypobaric hypoxia (CIHH) has demonstrated neuroprotective efficacy in several neurological disease models. In the present study, we
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Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-22 Hongfei Ge; Chao Zhang; Yang Yang; Weixiang Chen; Jun Zhong; Xuanyu Fang; Xuheng Jiang; Liang Tan; Yongjie Zou; Rong Hu; Yujie Chen; Hua Feng
Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery
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Gonadal Cycle-Dependent Expression of Genes Encoding Peptide-, Growth Factor-, and Orphan G-Protein-Coupled Receptors in Gonadotropin- Releasing Hormone Neurons of Mice Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-30 Csaba Vastagh; Veronika Csillag; Norbert Solymosi; Imre Farkas; Zsolt Liposits
Rising serum estradiol triggers the surge release of gonadotropin-releasing hormone (GnRH) at late proestrus leading to ovulation. We hypothesized that proestrus evokes alterations in peptidergic signaling onto GnRH neurons inducing a differential expression of neuropeptide-, growth factor-, and orphan G-protein-coupled receptor (GPCR) genes. Thus, we analyzed the transcriptome of GnRH neurons collected
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Transmembrane Collagens in Neuromuscular Development and Disorders Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-28 Tomoko Wakabayashi
Neuromuscular development is a multistep process and involves interactions among various extracellular and transmembrane molecules that facilitate the precise targeting of motor axons to synaptogenic regions of the target muscle. Collagenous proteins with transmembrane domains have recently emerged as molecules that play essential roles in multiple aspects of neuromuscular formation. Membrane-associated
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The Molecular Mechanism of Chronic High-Dose Corticosterone-Induced Aggravation of Cognitive Impairment in APP/PS1 Transgenic Mice Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-17 Shen-Qing Zhang; Long-Long Cao; Yun-Yue Liang; Pu Wang
Clinical studies have found that some Alzheimer’s disease (AD) patients suffer from Cushing’s syndrome (CS). CS is caused by the long-term release of excess glucocorticoids (GCs) from the adrenal gland, which in turn, impair brain function and induce dementia. Thus, we investigated the mechanism of the effect of corticosterone (CORT) on the development and progression of AD in a preclinical model.
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Novel Phosphorylation-State Specific Antibodies Reveal Differential Deposition of Ser26 Phosphorylated Aβ Species in a Mouse Model of Alzheimer’s Disease Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-15 Sathish Kumar; Akshay Kapadia; Sandra Theil; Pranav Joshi; Florian Riffel; Michael T. Heneka; Jochen Walter
Aggregation and deposition of amyloid-β (Aβ) peptides in extracellular plaques and in the cerebral vasculature are prominent neuropathological features of Alzheimer’s disease (AD) and closely associated with the pathogenesis of AD. Amyloid plaques in the brains of most AD patients and transgenic mouse models exhibit heterogeneity in the composition of Aβ deposits, due to the occurrence of elongated
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The Synaptic Dysregulation in Adolescent Rats Exposed to Maternal Immune Activation Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-27 Magdalena Cieślik; Magdalena Gassowska-Dobrowolska; Aleksandra Zawadzka; Małgorzata Frontczak-Baniewicz; Magdalena Gewartowska; Agnieszka Dominiak; Grzegorz A. Czapski; Agata Adamczyk
Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders in offspring, but the pathomechanism is largely unknown. The aim of our study was to analyse the molecular mechanisms contributing to synaptic alterations in hippocampi of adolescent rats exposed prenatally to MIA. MIA was evoked in pregnant female rats by i.p. administration of lipopolysaccharide at gestation day 9
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The Role of Cathepsin B in the Degradation of Aβ and in the Production of Aβ Peptides Starting With Ala2 in Cultured Astrocytes Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-03 Timo Jan Oberstein; Janine Utz; Philipp Spitzer; Hans Wolfgang Klafki; Jens Wiltfang; Piotr Lewczuk; Johannes Kornhuber; Juan Manuel Maler
Astrocytes may not only be involved in the clearance of Amyloid beta peptides (Aβ) in Alzheimer's disease (AD), but appear to produce N-terminally truncated Aβ (Aβn−x) independently of BACE1, which generates the N-Terminus of Aβ starting with Asp1 (Aβ1−x). A candidate protease for the generation of Aβn−x is cathepsin B (CatB), especially since CatB has also been reported to degrade Aβ, which could
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Upregulation of Spinal ASIC1 and NKCC1 Expression Contributes to Chronic Visceral Pain in Rats Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-15 Yong-Chang Li; Yuan-Qing Tian; Yan-Yan Wu; Yu-Cheng Xu; Ping-An Zhang; Jie Sha; Guang-Yin Xu
Aims: To determine whether acid-sensing ion channel 1 (ASIC1)–sodium-potassium-chloride cotransporter 1 (NKCC1) signaling pathway participates in chronic visceral pain of adult rats with neonatal maternal deprivation (NMD). Methods: Chronic visceral pain was detected by colorectal distension (CRD). Western blotting and Immunofluorescence were performed to detect the expression and location of ASIC1
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AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-11 Simon J. O’Carroll; William H. Cook; Deborah Young
Different glial cell types are found throughout the central (CNS) and peripheral nervous system (PNS), where they have important functions. These cell types are also involved in nervous system pathology, playing roles in neurodegenerative disease and following trauma in the brain and spinal cord (astrocytes, microglia, oligodendrocytes), nerve degeneration and development of pain in peripheral nerves
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Quantification of Huntington’s Disease Related Markers in the R6/2 Mouse Model Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-10 Estibaliz Etxeberria-Rekalde; Saioa Alzola-Aldamizetxebarria; Stefanie Flunkert; Isabella Hable; Magdalena Daurer; Joerg Neddens; Birgit Hutter-Paier
Huntington’s disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result in a devasting and lethal phenotype. Neurodegeneration in HD begins in the striatum and spreads to other brain regions such as cortex and hippocampus, causing motor and cognitive dysfunctions. To understand the signaling pathways involved in HD, animal
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The Neomycin Resistance Cassette in the Targeted Allele of Shank3B Knock-Out Mice Has Potential Off-Target Effects to Produce an Unusual Shank3 Isoform Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-02 Chunmei Jin; Hyojin Kang; Taesun Yoo; Jae Ryun Ryu; Ye-Eun Yoo; Ruiying Ma; Yinhua Zhang; Hyae Rim Kang; Yoonhee Kim; Hyunyoung Seong; Geul Bang; Sangwoo Park; Seok-Kyu Kwon; Woong Sun; Hyunkyung Kim; Jin Young Kim; Eunjoon Kim; Kihoon Han
Variants of the SH3 and multiple ankyrin repeat domains 3 (SHANK3), which encodes postsynaptic scaffolds, are associated with brain disorders. The targeted alleles in a few Shank3 knock-out (KO) lines contain a neomycin resistance (Neo) cassette, which may perturb the normal expression of neighboring genes; however, this has not been investigated in detail. We previously reported an unexpected increase
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Effects of Constitutive and Acute Connexin 36 Deficiency on Brain-Wide Susceptibility to PTZ-Induced Neuronal Hyperactivity Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-25 Alyssa A. Brunal; Kareem C. Clark; Manxiu Ma; Ian G. Woods; Y. Albert Pan
Connexins are transmembrane proteins that form hemichannels allowing the exchange of molecules between the extracellular space and the cell interior. Two hemichannels from adjacent cells dock and form a continuous gap junction pore, thereby permitting direct intercellular communication. Connexin 36 (Cx36), expressed primarily in neurons, is involved in the synchronous activity of neurons and may play
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Neuroproteomics in Epilepsy: What Do We Know so Far? Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-09 Amanda M. do Canto; Amanda Donatti; Jaqueline C. Geraldis; Alexandre B. Godoi; Douglas C. da Rosa; Iscia Lopes-Cendes
Epilepsies are chronic neurological diseases that affect approximately 2% of the world population. In addition to being one of the most frequent neurological disorders, treatment for patients with epilepsy remains a challenge, because a proportion of patients do not respond to the antiseizure medications that are currently available. This results in a severe economic and social burden for patients
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Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-04 Vladan Rankovic; Christian Vogl; Nele M. Dörje; Iman Bahader; Carlos J. Duque-Afonso; Anupriya Thirumalai; Thomas Weber; Kathrin Kusch; Nicola Strenzke; Tobias Moser
Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of
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Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-01 Audrey Hector; Jonathan Brouillette
Soluble amyloid-beta oligomers (Aβo) start to accumulate in the human brain one to two decades before any clinical symptoms of Alzheimer's disease (AD) and are implicated in synapse loss, one of the best predictors of memory decline that characterize the illness. Cognitive impairment in AD was traditionally thought to result from a reduction in synaptic activity which ultimately induces neurodegeneration
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Neuroinflammation in Ischemic Stroke: Focus on MicroRNA-mediated Polarization of Microglia Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-30 Lu Lian; Yunsha Zhang; Lu Liu; Liji Yang; Yichen Cai; Junping Zhang; Shixin Xu
Ischemic stroke is one of the most common causes of death and disability worldwide. Neuroinflammation is a major pathological event involved in the process of ischemic injury and repair. In particular, microglia play a dual role in neuroinflammation. During the acute phase of stroke onset, M2 microglia are the dominant phenotype and exert protective effects on neuronal cells, whereas permanent M1 microglia
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Enrichment and Correlation Analysis of Serum miRNAs in Comorbidity Between Arnold-Chiari and Tourette Syndrome Contribute to Clarify Their Molecular Bases Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-04 Federica Mirabella; Mariangela Gulisano; Mara Capelli; Giovanni Lauretta; Matilde Cirnigliaro; Stefano Palmucci; Michele Stella; Davide Barbagallo; Cinzia Di Pietro; Michele Purrello; Marco Ragusa; Renata Rizzo
Due to its rarity, coupled to a multifactorial and very heterogeneous nature, the molecular etiology of Arnold-Chiari (AC) syndrome remains almost totally unknown. Its relationship with other neuropsychiatric disorders such as Tourette syndrome (TS) is also undetermined. The rare comorbid status between both disorders (ACTS) complicates the framework of diagnosis and negatively affects the patients'
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Ndfip1 Prevents Rotenone-Induced Neurotoxicity and Upregulation of α-Synuclein in SH-SY5Y Cells Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-02 Xin Liu; Le Qu; Na Zhang; Xiaoqi Yu; Zhixin Xiao; Limei Song; Junxia Xie; Huamin Xu
Nedd4 family interacting protein 1 (Ndfip1) is an adaptor of Nedd4-family ubiquitin ligases. Experimental results showed that Ndfip1 had a potential neuroprotective effect in neurology diseases. However, the neuroprotective effect and the underlying mechanisms of Ndfip1 in Parkinson's disease (PD) have not yet been fully elucidated. Therefore, in this study, we explored the neuroprotective effect of
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Recent Developments in Data Independent Acquisition (DIA) Mass Spectrometry: Application of Quantitative Analysis of the Brain Proteome Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-02 Ka Wan Li; Miguel A. Gonzalez-Lozano; Frank Koopmans; August B. Smit
Mass spectrometry is the driving force behind current brain proteome analysis. In a typical proteomics approach, a protein isolate is digested into tryptic peptides and then analyzed by liquid chromatography–mass spectrometry. The recent advancements in data independent acquisition (DIA) mass spectrometry provide higher sensitivity and protein coverage than the classic data dependent acquisition. DIA
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Target Molecules of STIM Proteins in the Central Nervous System Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-12-02 Karolina Serwach; Joanna Gruszczynska-Biegala
Stromal interaction molecules (STIMs), including STIM1 and STIM2, are single-pass transmembrane proteins that are located predominantly in the endoplasmic reticulum (ER). They serve as calcium ion (Ca2+) sensors within the ER. In the central nervous system (CNS), they are involved mainly in Orai-mediated store-operated Ca2+ entry (SOCE). The key molecular components of the SOCE pathway are well-characterized
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GABA Measurement in a Neonatal Fragile X Syndrome Mouse Model Using 1H-Magnetic Resonance Spectroscopy and Mass Spectrometry Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-20 Samantha T. Reyes; Sanaz Mohajeri; Karolina Krasinska; Scarlett G. Guo; Meng Gu; Laura Pisani; Jarrett Rosenberg; Daniel M. Spielman; Frederick T. Chin
Fragile X syndrome (FXS) is the leading monogenetic cause of autism spectrum disorder and inherited cause of intellectual disability that affects approximately one in 7,000 males and one in 11,000 females. In FXS, the Fmr1 gene is silenced and prevents the expression of the fragile X mental retardation protein (FMRP) that directly targets mRNA transcripts of multiple GABAA subunits. Therefore, FMRP
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Modulation of the Acetylcholine Receptor Clustering Pathway Improves Neuromuscular Junction Structure and Muscle Strength in a Mouse Model of Congenital Myasthenic Syndrome Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-24 Sally Spendiff; Rachel Howarth; Grace McMacken; Tracey Davey; Kaitlyn Quinlan; Emily O'Connor; Clarke Slater; Stefan Hettwer; Armin Mäder; Andreas Roos; Rita Horvath; Hanns Lochmüller
Introduction: Congenital myasthenic syndromes (CMS) are a diverse group of inherited neuromuscular disorders characterized by a failure of synaptic transmission at the neuromuscular junction (NMJ). CMS often present early with fatigable weakness and can be fatal through respiratory complications. The AGRN gene is one of over 30 genes known to harbor mutations causative for CMS. In this study, we aimed
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Acetylcholine Muscarinic Receptors in Ventral Hippocampus Modulate Stress-Induced Anxiety-Like Behaviors in Mice Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-18 Li Mei; Yu Zhou; Yi Sun; Hong Liu; Dengwen Zhang; Pingping Liu; Haihua Shu
Chronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The ventral hippocampus (vHPC) is central to affective and cognitive processing and displays a high density of acetylcholine (ACh) muscarinic receptors (mAChRs). However, the precise role of vHPC mAChRs in anxiety remains to be fully investigated. In this study, we found that chronic restraint stress (CRS)
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Molecular Imaging of Tau Protein: New Insights and Future Directions Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-16 Rocco Pizzarelli; Natalia Pediconi; Silvia Di Angelantonio
Tau is a microtubule-associated protein (MAPT) that is highly expressed in neurons and implicated in several cellular processes. Tau misfolding and self-aggregation give rise to proteinaceous deposits known as neuro-fibrillary tangles. Tau tangles play a key role in the genesis of a group of diseases commonly referred to as tauopathies; notably, these aggregates start to form decades before any clinical
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Modulation of the Mechanisms Driving Transthyretin Amyloidosis Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-18 Filipa Bezerra; Maria João Saraiva; Maria Rosário Almeida
Transthyretin (TTR) amyloidoses are systemic diseases associated with TTR aggregation and extracellular deposition in tissues as amyloid. The most frequent and severe forms of the disease are hereditary and associated with amino acid substitutions in the protein due to single point mutations in the TTR gene (ATTRv amyloidosis). However, the wild type TTR (TTR wt) has an intrinsic amyloidogenic potential
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Abnormal Levels of Metal Micronutrients and Autism Spectrum Disorder: A Perspective Review Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-20 Supriya Behl; Sunil Mehta; Mukesh K. Pandey
The aim of the present review is to summarize the prevalence of abnormal levels of various metal micronutrients including copper (Cu), iron (Fe), magnesium (Mg), zinc (Zn), and selenium (Se) in Autism Spectrum Disorder (ASD) using hair, nail and serum samples. A correlation of selected abnormal metal ions with known neurodevelopmental processes using Gene Ontology (GO) term was also conducted. Data
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Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy: Preclinical Data in Rats Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-11 Julia Alicja Szczygieł; Kira Iben Danielsen; Esbjörn Melin; Søren Hofman Rosenkranz; Stanislava Pankratova; Annika Ericsson; Karin Agerman; Merab Kokaia; David Paul Drucker Woldbye
Gene therapy to treat pharmacoresistant temporal lobe epilepsy in humans is now being developed using an AAV vector (CG01) that encodes the combination of neuropeptide Y and its antiepileptic receptor Y2. With this in mind, the present study aimed to provide important preclinical data on the effects of CG01 on the duration of transgene expression, cellular tropism, and potential side effects on body
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New Insights Into Drug Discovery Targeting Tau Protein Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-10 Yoshiyuki Soeda; Akihiko Takashima
Microtubule-associated protein tau is characterized by the fact that it is an intrinsically disordered protein due to its lack of a stable conformation and high flexibility. Intracellular inclusions of fibrillar forms of tau with a β-sheet structure accumulate in the brain of patients with Alzheimer's disease and other tauopathies. Accordingly, detachment of tau from microtubules and transition of
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The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-30 Pedro M. Rodríguez Cruz; Judith Cossins; David Beeson; Angela Vincent
The neuromuscular junction (NMJ) is a highly specialized synapse between a motor neuron nerve terminal and its muscle fiber that are responsible for converting electrical impulses generated by the motor neuron into electrical activity in the muscle fibers. On arrival of the motor nerve action potential, calcium enters the presynaptic terminal, which leads to the release of the neurotransmitter acetylcholine
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Neurogenetic and Neuroepigenetic Mechanisms in Cognitive Health and Disease Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-05 Davide Martino Coda; Johannes Gräff
Over the last two decades, the explosion of experimental, computational, and high-throughput technologies has led to critical insights into how the brain functions in health and disease. It has become increasingly clear that the vast majority of brain activities result from the complex entanglement of genetic factors, epigenetic changes, and environmental stimuli, which, when altered, can lead to neurodegenerative
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The Q336H MAPT Mutation Linked to Pick’s Disease Leads to Increased Binding of Tau to the Microtubule Network via Altered Conformational and Phosphorylation Effects Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-09 Giacomo Siano; Mariachiara Micaelli; Arianna Scarlatti; Valentina Quercioli; Cristina Di Primio; Antonino Cattaneo
Tauopathies are neurodegenerative disorders characterized by Tau aggregation. Genetic studies on familial cases allowed for the discovery of mutations in the MAPT gene that increase Tau propensity to detach from microtubules and to form insoluble cytoplasmic Tau aggregates. Recently, the rare mutation Q336H has been identified to be associated with Pick’s disease (PiD) and biochemical analyses demonstrated
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Hypoxia-Ischemia Induced Age-Dependent Gene Transcription Effects at Two Development Stages in the Neonate Mouse Brain Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-19 Nicolas Dupré; Céline Derambure; Bérénice Le Dieu-Lugon; Michelle Hauchecorne; Yannick Detroussel; Bruno J. Gonzalez; Stéphane Marret; Philippe Leroux
Human brain lesions in the perinatal period result in life-long neuro-disabilities impairing sensory-motor, cognitive, and behavior functions for years. Topographical aspects of brain lesions depend on gestational age at the time of insult in preterm or term infants and impaired subsequent steps of brain development and maturation. In mice, the Rice-Vannucci procedure of neonate hypoxia-ischemia (HI)
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MIRRAGGE – Minimum Information Required for Reproducible AGGregation Experiments Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-23 Pedro M. Martins; Susanna Navarro; Alexandra Silva; Maria F. Pinto; Zsuzsa Sárkány; Francisco Figueiredo; Pedro José Barbosa Pereira; Francisca Pinheiro; Zuzana Bednarikova; Michał Burdukiewicz; Oxana V. Galzitskaya; Zuzana Gazova; Cláudio M. Gomes; Annalisa Pastore; Louise C. Serpell; Rostislav Skrabana; Vytautas Smirnovas; Mantas Ziaunys; Daniel E. Otzen; Salvador Ventura; Sandra Macedo-Ribeiro
Reports on phase separation and amyloid formation for multiple proteins and aggregation-prone peptides are recurrently used to explore the molecular mechanisms associated with several human diseases. The information conveyed by these reports can be used directly in translational investigation, e.g., for the design of better drug screening strategies, or be compiled in databases for benchmarking novel
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A Functional Comparison of Homopentameric Nicotinic Acetylcholine Receptors (ACR-16) Receptors From Necator americanus and Ancylostoma ceylanicum Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-04 Mark D. Kaji; Timothy G. Geary; Robin N. Beech
Effective control of hookworm infections in humans and animals relies on using a small group of anthelmintics. Many of these drugs target cholinergic ligand-gated ion channels, yet the direct activity of anthelmintics has only been studied in a subset of these receptors, primarily in the non-parasitic nematode, Caenorhabditis elegans. Here we report the characterization of a homopentameric ionotropic
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Modulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-03 Madeleine R. Brown; Sheena E. Radford; Eric W. Hewitt
Amyloid plaques are a pathological hallmark of Alzheimer’s disease. The major component of these plaques are highly ordered amyloid fibrils formed by amyloid-β (Aβ) peptides. However, whilst Aβ amyloid fibril assembly has been subjected to detailed and extensive analysis in vitro, these studies may not reproduce how Aβ fibrils assemble in the brain. This is because the brain represents a highly complex
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A Neurotoxic Ménage-à-trois: Glutamate, Calcium, and Zinc in the Excitotoxic Cascade Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-30 Alberto Granzotto; Lorella M. T. Canzoniero; Stefano L. Sensi
Fifty years ago, the seminal work by John Olney provided the first evidence of the neurotoxic properties of the excitatory neurotransmitter glutamate. A process hereafter termed excitotoxicity. Since then, glutamate-driven neuronal death has been linked to several acute and chronic neurological conditions, like stroke, traumatic brain injury, Alzheimer’s, Parkinson’s, and Huntington’s diseases, and
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Local Secretory Trafficking Pathways in Neurons and the Role of Dendritic Golgi Outposts in Different Cell Models Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-19 Jingqi Wang; Lou Fourriere; Paul A. Gleeson
A fundamental characteristic of neurons is the relationship between the architecture of the polarized neuron and synaptic transmission between neurons. Intracellular membrane trafficking is paramount to establish and maintain neuronal structure; perturbation in trafficking results in defects in neurodevelopment and neurological disorders. Given the physical distance from the cell body to the distal
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Adult Mouse Retina Explants: From ex vivo to in vivo Model of Central Nervous System Injuries Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-16 Julia Schaeffer; Céline Delpech; Floriane Albert; Stephane Belin; Homaira Nawabi
In mammals, adult neurons fail to regenerate following any insult to adult central nervous system (CNS), which leads to a permanent and irreversible loss of motor and cognitive functions. For a long time, much effort has been deployed to uncover mechanisms of axon regeneration in the CNS. Even if some cases of functional recovery have been reported, there is still a discrepancy regarding the functionality
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Effects of GABAA Receptor α3 Subunit Epilepsy Mutations on Inhibitory Synaptic Signaling Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-11-02 Parnayan Syed; Nela Durisic; Robert J. Harvey; Pankaj Sah; Joseph W. Lynch
Missense mutations T166M, Q242L, T336M, and Y474C in the GABAA receptor (GABAAR) α3 subunit gene are associated with epileptic seizures, dysmorphic features, intellectual disability, and developmental delay. When incorporated into GABAARs expressed in oocytes, all mutations are known to reduce GABA-evoked whole-cell currents. However, their impact on the properties of inhibitory synaptic currents (IPSCs)
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Neuroinflammation-Induced Upregulation of Glial Cathepsin X Expression and Activity in vivo Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-28 Anja Pišlar; Larisa Tratnjek; Gordana Glavan; Nace Zidar; Marko Živin; Janko Kos
Neuroinflammation is an important factor in the pathogenesis of neurodegenerative diseases. Microglia-derived lysosomal cathepsins have been increasingly recognized as important inflammatory mediators that trigger signaling pathways that aggravate neuroinflammation. In vitro, a contribution to neuroinflammation processes has been shown for cathepsin X: however, the expression patterns and functional
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The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-22 Leah A. Owen; Kinsey Shirer; Samuel A. Collazo; Kathryn Szczotka; Shawna Baker; Blair Wood; Lara Carroll; Benjamin Haaland; Takeshi Iwata; Lakshmi D. Katikaneni; Margaret M. DeAngelis
Retinopathy of prematurity (ROP) is a blinding aberrancy of retinal vascular maturation in preterm infants. Despite delayed onset after preterm birth, representing a window for therapeutic intervention, we cannot prevent or cure ROP blindness. A natural form of ROP protection exists in the setting of early-onset maternal preeclampsia, though is not well characterized. As ischemia is a central feature
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How Microglia Manages Non-cell Autonomous Vicious Cycling of Aβ Toxicity in the Pathogenesis of AD Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-20 YunHee Seol; Soomin Ki; Hannah L. Ryu; Sooyoung Chung; Junghee Lee; Hoon Ryu
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and a common form of dementia that affects cognition and memory mostly in aged people. AD pathology is characterized by the accumulation of β-amyloid (Aβ) senile plaques and the neurofibrillary tangles of phosphorylated tau, resulting in cell damage and neurodegeneration. The extracellular deposition of Aβ is regarded as an important
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Loss of DEK Expression Induces Alzheimer’s Disease Phenotypes in Differentiated SH-SY5Y Cells Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-20 Allie N. Greene; Lois G. Parks; Matia B. Solomon; Lisa M. Privette Vinnedge
Alzheimer’s disease (AD) is the most common cause of dementia and is characterized by the buildup of β-amyloid plaques and neurofibrillary Tau tangles. This leads to decreased synaptic efficacy, cell death, and, consequently, brain atrophy in patients. Behaviorally, this manifests as memory loss and confusion. Using a gene ontology analysis, we recently identified AD and other age-related dementias
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Impairment Mechanisms and Intervention Approaches for Aged Human Neuromuscular Junctions Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-16 Yomna Badawi; Hiroshi Nishimune
The neuromuscular junction (NMJ) is a chemical synapse formed between a presynaptic motor neuron and a postsynaptic muscle cell. NMJs in most vertebrate species share many essential features; however, some differences distinguish human NMJs from others. This review will describe the pre- and postsynaptic structures of human NMJs and compare them to NMJs of laboratory animals. We will focus on age-dependent
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Nicotine Prevents Oxidative Stress-Induced Hippocampal Neuronal Injury Through α7-nAChR/Erk1/2 Signaling Pathway Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-01 Yun Dong; Wenchuan Bi; Kai Zheng; Enni Zhu; Shaoxiang Wang; Yiping Xiong; Junlei Chang; Jianbing Jiang; Bingfeng Liu; Zhonghua Lu; Yongxian Cheng
Oxidative stress-induced neuronal damage has been implicated to play a dominant role in neurodegenerative disorders, such as Alzheimer’s disease (AD). Nicotine, a principal additive compound for tobacco users, is thought as a candidate to attenuate amyloid-β-mediated neurotoxicity and NMDA-induced excitotoxicity. Previous studies demonstrated that nicotine exerted this neuroprotective action on oxidative
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Amyloid-β Peptide Impact on Synaptic Function and Neuroepigenetic Gene Control Reveal New Therapeutic Strategies for Alzheimer’s Disease Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-22 Bhanu Chandra Karisetty; Akanksha Bhatnagar; Ellen M. Armour; Mariah Beaver; Haolin Zhang; Felice Elefant
Amyloid-β (Aβ) peptides can form protease-resistant aggregates within and outside of neurons. Accumulation of these aggregates is a hallmark of Alzheimer’s disease (AD) neuropathology and contributes to devastating cognitive deficits associated with this disorder. The primary etiological factor for Aβ aggregation is either an increase in Aβ production or a decrease in its clearance. Aβ is produced
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Quantitative Changes in the Mitochondrial Proteome of Cerebellar Synaptosomes From Preclinical Cystatin B-Deficient Mice Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-21 Katarin Gorski; Albert Spoljaric; Tuula A. Nyman; Kai Kaila; Brendan J. Battersby; Anna-Elina Lehesjoki
Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is a neurodegenerative disorder caused by loss-of-function mutations in the cystatin B (CSTB) gene. Progression of the clinical symptoms in EPM1 patients, including stimulus-sensitive myoclonus, tonic-clonic seizures, and ataxia, are well described. However, the cellular dysfunction during the presymptomatic phase that precedes the disease
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Krüppel-Like Factors 9 and 13 Block Axon Growth by Transcriptional Repression of Key Components of the cAMP Signaling Pathway Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-21 José Ávila-Mendoza; Arasakumar Subramani; Robert J. Denver
Krüppel-like factors (KLFs) are zinc finger transcription factors implicated in diverse biological processes, including differentiation of neural cells. The ability of mammalian neurons to elongate axons decreases during postnatal development in parallel with a decrease in cAMP, and increase in expression of several Klf genes. The paralogous KLFs 9 and 13 inhibit neurite outgrowth, and we hypothesized
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Cell Adhesion Molecules and Protein Synthesis Regulation in Neurons Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-16 Irina Kozlova; Saroj Sah; Ryan Keable; Iryna Leshchyns’ka; Michael Janitz; Vladimir Sytnyk
Cell adhesion molecules (CAMs) mediate interactions of neurons with the extracellular environment by forming adhesive bonds with CAMs on adjacent membranes or via binding to proteins of the extracellular matrix. Binding of CAMs to their extracellular ligands results in the activation of intracellular signaling cascades, leading to changes in neuronal structure and the molecular composition and function
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Using Zebrafish to Model Autism Spectrum Disorder: A Comparison of ASD Risk Genes Between Zebrafish and Their Mammalian Counterparts Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-08 Victoria Rea; Terence J. Van Raay
Autism spectrum disorders (ASDs) are a highly variable and complex set of neurological disorders that alter neurodevelopment and cognitive function, which usually presents with social and learning impairments accompanied with other comorbid symptoms like hypersensitivity or hyposensitivity, or repetitive behaviors. Autism can be caused by genetic and/or environmental factors and unraveling the etiology
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P2X7 Receptor-Dependent Layer-Specific Changes in Neuron-Microglia Reactivity in the Prefrontal Cortex of a Phencyclidine Induced Mouse Model of Schizophrenia Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-09-30 Stefano Calovi; Paula Mut-Arbona; Pál Tod; András Iring; Annette Nicke; Susana Mato; E. Sylvester Vizi; Jan Tønnesen; Beata Sperlagh
Background: It has been consistently reported that the deficiency of the adenosine triphosphate (ATP) sensitive purinergic receptor P2X7 (P2X7R) ameliorates symptoms in animal models of brain diseases. Objective: This study aimed to investigate the role of P2X7R in rodent models of acute and subchronic schizophrenia based on phencyclidine (PCP) delivery in animals lacking or overexpressing P2X7R, and
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Plasma Exosomal MiRNAs Expression Profile in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis: Case-Control Study and Analysis of Potential Functions Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-16 Li-Gang Huang; Yun-He Luo; Ji-Wen Xu; Qin-Chi Lu
Background To explore an expression profile in plasma exosomal miRNAs of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE + HS) patients and investigate the associated clinical significance and putative pathways involved. Methods Plasma exosomal miRNAs were measured in six mTLE + HS patients who were confirmed with pre-surgical stereo-electroencephalography and six without hippocampal
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The Interplay Between Beta-Amyloid 1–42 (Aβ1–42)-Induced Hippocampal Inflammatory Response, p-tau, Vascular Pathology, and Their Synergistic Contributions to Neuronal Death and Behavioral Deficits Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-09-22 Beatriz Calvo-Flores Guzmán; Tessa Elizabeth Chaffey; Thulani Hansika Palpagama; Sarah Waters; Jordi Boix; Warren Perry Tate; Katie Peppercorn; Michael Dragunow; Henry John Waldvogel; Richard Lewis Maxwell Faull; Andrea Kwakowsky
Alzheimer’s disease (AD), the most common chronic neurodegenerative disorder, has complex neuropathology. The principal neuropathological hallmarks of the disease are the deposition of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) comprised of hyperphosphorylated tau (p-tau) protein. These changes occur with neuroinflammation, a compromised blood-brain barrier (BBB) integrity
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LRR-Containing Oncofetal Trophoblast Glycoprotein 5T4 Shapes Neural Circuits in Olfactory and Visual Systems Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-09-22 Akio Tsuboi
In mammals, the sensory experience can regulate the development of various brain structures, including the cortex, hippocampus, retina, and olfactory bulb (OB). Odor experience-evoked neural activity drives the development of dendrites on excitatory projection neurons in the OB, such as mitral and tufted cells, as well as inhibitory interneurons. OB interneurons are generated continuously in the subventricular
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Effects of CYP46A1 Inhibition on Long-Term-Depression in Hippocampal Slices ex vivo and 24S-Hydroxycholesterol Levels in Mice in vivo Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-10-06 Michael Popiolek; Yukitoshi Izumi; Allen T. Hopper; Jing Dai; Silke Miller; Hong-Jin Shu; Charles F. Zorumski; Steven Mennerick
The manipulation of cholesterol and its metabolites has been hypothesized to be therapeutically beneficial for mood disorders, neurodegenerative disorders, and epilepsies. A major regulator of cholesterol clearance and turnover in the central nervous system is CYP46A1, a brain enriched enzyme responsible for metabolism of cholesterol into 24S-hydroxycholesterol. Inhibition of this enzyme may negatively
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Enhanced Prefrontal Neuronal Activity and Social Dominance Behavior in Postnatal Forebrain Excitatory Neuron-Specific Cyfip2 Knock-Out Mice Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-09-29 Yinhua Zhang; Rim Kang Hyae; Seung-Hyun Lee; Yoonhee Kim; Ruiying Ma; Chunmei Jin; Ji-Eun Lim; Seoyeon Kim; Yeju Kang; Hyojin Kang; Su Yeon Kim; Seok-Kyu Kwon; Se-Young Choi; Kihoon Han
The cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2) gene is associated with epilepsy, intellectual disability (ID), and developmental delay, suggesting its critical role in proper neuronal development and function. CYFIP2 is involved in regulating cellular actin dynamics and also interacts with RNA-binding proteins. However, the adult brain function of CYFIP2 remains
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Functional Interactions of Tau Phosphorylation Sites That Mediate Toxicity and Deficient Learning in Drosophila melanogaster Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-09-15 Iason Keramidis; Ergina Vourkou; Katerina Papanikolopoulou; Efthimios M. C. Skoulakis
Hyperphosphorylated Tau protein is the main component of the neurofibrillary tangles, characterizing degenerating neurons in Alzheimer’s disease and other Tauopathies. Expression of human Tau protein in Drosophila CNS results in increased toxicity, premature mortality and learning and memory deficits. Herein we use novel transgenic lines to investigate the contribution of specific phosphorylation sites
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Neuronal Activity at Synapse Resolution: Reporters and Effectors for Synaptic Neuroscience Front. Mol. Neurosci. (IF 4.057) Pub Date : 2020-08-31 Francesco Gobbo; Antonino Cattaneo
The development of methods for the activity-dependent tagging of neurons enabled a new way to tackle the problem of engram identification at the cellular level, giving rise to groundbreaking findings in the field of memory studies. However, the resolution of activity-dependent tagging remains limited to the whole-cell level. Notably, events taking place at the synapse level play a critical role in