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Frontiers in Molecular Neuroscience

Xian Li, Shurui Chen, Liang Mao, Daoyong Li, Chang Xu, He Tian, Xifan Mei
While zinc promotes motor function recovery after spinal cord injury (SCI), the precise mechanisms involved are not fully understood. The present study aimed to elucidate the effects of zinc and granulocyte colony stimulating factor (G-CSF) on neuronal recovery after SCI. The SCI model was established by Allen's method. Injured animals were given glucose and zinc gluconate (ZnG; 30 mg/kg) for the first time at 2 h after injury, the same dose was given for 3 days. A cytokine antibody array was used to screen changes in inflammation at the site of SCI lesion...
2019: Frontiers in Molecular Neuroscience
João Fonseca-Gomes, André Jerónimo-Santos, Angelina Lesnikova, Plinio Casarotto, Eero Castrén, Ana M Sebastião, Maria J Diógenes
The signaling of brain-derived neurotrophic factor (BDNF) has been suggested to be impaired in Alzheimer's disease (AD), which may compromise the function of BDNF upon neuronal activity and survival. Accordingly, decreased levels of BDNF and its tropomyosin-receptor kinase B-full-length (TrkB-FL) have been detected in human brain samples of AD patients. We have previously found that neuronal exposure to amyloid-β (Aβ) peptide, a hallmark of AD, leads to calpain overactivation and subsequent TrkB-FL cleavage leading to decreased levels of TrkB-FL and the generation of two new fragments: a membrane-bound truncated receptor (TrkB-T') and an intracellular fragment (TrkB-ICD)...
2019: Frontiers in Molecular Neuroscience
Xue Wu, Mei Ding, Yi Liu, Xi Xia, Feng-Ling Xu, Jun Yao, Bao-Jie Wang
Abnormal expression of the 5-HT1A receptor, which is encoded by the HTR1A gene, leads to susceptibilities to neuropsychiatric disorders such as depression, anxiety, and schizophrenia. miRNAs regulate gene expression by recognizing the 3'-UTR region of mRNA. This study evaluated the miRNAs that might identify and subsequently determine the regulatory mechanism of HTR1A gene. Using the HEK-293, U87, SK-N-SH and SH-SY5Y cell lines, we determined the functional sequence of the 3'-UTR region of the HTR1A gene and predicted miRNA binding...
2019: Frontiers in Molecular Neuroscience
Lucas Matt, Karam Kim, Dhrubajyoti Chowdhury, Johannes W Hell
Many postsynaptic proteins undergo palmitoylation, the reversible attachment of the fatty acid palmitate to cysteine residues, which influences trafficking, localization, and protein interaction dynamics. Both palmitoylation by palmitoyl acyl transferases (PAT) and depalmitoylation by palmitoyl-protein thioesterases (PPT) is regulated in an activity-dependent, localized fashion. Recently, palmitoylation has received attention for its pivotal contribution to various forms of synaptic plasticity, the dynamic modulation of synaptic strength in response to neuronal activity...
2019: Frontiers in Molecular Neuroscience
John Inge Johnsen, Cecilia Dyberg, Malin Wickström
Neuroblastoma is a neural crest derived malignancy of the peripheral nervous system and is the most common and deadliest tumor of infancy. It is characterized by clinical heterogeneity with a disease spectrum ranging from spontaneous regression without any medical intervention to treatment resistant tumors with metastatic spread and poor patient survival. The events that lead to the development of neuroblastoma from the neural crest have not been fully elucidated. Here we discuss factors and processes within the neural crest that when dysregulated have the potential to be initiators or drivers of neuroblastoma development...
2019: Frontiers in Molecular Neuroscience
Maria Eleni Kastriti, Polina Kameneva, Dmitry Kamenev, Viacheslav Dyachuk, Alessandro Furlan, Marek Hampl, Fatima Memic, Ulrika Marklund, Francois Lallemend, Saida Hadjab, Laura Calvo-Enrique, Patrik Ernfors, Kaj Fried, Igor Adameyko
In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases...
2019: Frontiers in Molecular Neuroscience
Yu-Peng Guo, Yu-Ru Zhi, Ting-Ting Liu, Yun Wang, Ying Zhang
The Ca2+ -binding protein Kv channel interacting protein 3 (KChIP3) or downstream regulatory element antagonist modulator (DREAM), a member of the neuronal calcium sensor (NCS) family, shows remarkable multifunctional properties. It acts as a transcriptional repressor in the nucleus and a modulator of ion channels or receptors, such as Kv4, NMDA receptors and TRPV1 channels on the cytomembrane. Previous studies of Kcnip3 -/- mice have indicated that KChIP3 facilitates pain hypersensitivity by repressing Pdyn expression in the spinal cord...
2019: Frontiers in Molecular Neuroscience
Luca Sala, Giovanni Cirillo, Gabriele Riva, Gabriele Romano, Carlo Giussani, Annamaria Cialdella, Antonio Todisco, Assunta Virtuoso, Maria Grazia Cerrito, Angela Bentivegna, Emanuela Grassilli, Antonio Ardizzoia, Emanuela Bonoldi, Roberto Giovannoni, Michele Papa, Marialuisa Lavitrano
Bruton's tyrosine-kinase (BTK) is a non-receptor tyrosine kinase recently associated with glioma tumorigenesis and a novel prognostic marker for poor survival in patients with glioma. The p65BTK is a novel BTK isoform involved in different pathways of drug resistance of solid tumors, thus we aimed to investigate the expression and the putative role of p65BTK in tumors of the central nervous system (CNS). We selected a large cohort of patients with glial tumors ( n = 71) and analyzed the expression of p65BTK in different histotypes and correlation with clinical parameters...
2019: Frontiers in Molecular Neuroscience
Ines Schoberleitner, Anna Mutti, Anupam Sah, Alexandra Wille, Francisco Gimeno-Valiente, Paolo Piatti, Maria Kharitonova, Luis Torres, Gerardo López-Rodas, Jeffrey J Liu, Nicolas Singewald, Christoph Schwarzer, Alexandra Lusser
Precise temporal and spatial regulation of gene expression in the brain is a prerequisite for cognitive processes such as learning and memory. Epigenetic mechanisms that modulate the chromatin structure have emerged as important regulators in this context. While posttranslational modification of histones or the modification of DNA bases have been examined in detail in many studies, the role of ATP-dependent chromatin remodeling factors (ChRFs) in learning- and memory-associated gene regulation has largely remained obscure...
2019: Frontiers in Molecular Neuroscience
Alfredo Bellon, Amelie Wegener, Adam R Lescallette, Michael Valente, Seung-Kwon Yang, Robert Gardette, Julien Matricon, Faycal Mouaffak, Paula Watts, Lene Vimeux, Jong K Yun, Yuka Imamura Kawasawa, Gary A Clawson, Elisabeta Blandin, Boris Chaumette, Therese M Jay, Marie-Odile Krebs, Vincent Feuillet, Anne Hosmalin
Despite progress, our understanding of psychiatric and neurological illnesses remains poor, at least in part due to the inability to access neurons directly from patients. Currently, there are in vitro models available but significant work remains, including the search for a less invasive, inexpensive and rapid method to obtain neuronal-like cells with the capacity to deliver reproducible results. Here, we present a new protocol to transdifferentiate human circulating monocytes into neuronal-like cells in 20 days and without the need for viral insertion or reprograming...
2018: Frontiers in Molecular Neuroscience
Hyo Kyeong Cha, Sooyoung Chung, Hye Young Lim, Jong-Wha Jung, Gi Hoon Son
Circadian rhythms regulate many biological processes and play fundamental roles in behavior, physiology, and metabolism. Such periodicity is critical for homeostasis because disruption or misalignment of the intrinsic rhythms is associated with the onset and progression of various human diseases and often directly leads to pathological states. Since the first identification of mammalian circadian clock genes, numerous genetic and biochemical studies have revealed the molecular basis of these cell-autonomous and self-sustainable rhythms...
2018: Frontiers in Molecular Neuroscience
Suk-Yu Yau, Luis Bettio, Jason Chiu, Christine Chiu, Brian R Christie
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. It is caused by the overexpansion of cytosine-guanine-guanine (CGG) trinucleotide in Fmr1 gene, resulting in complete loss of the fragile X mental retardation protein (FMRP). Previous studies using Fmr1 knockout ( Fmr1 KO) mice have suggested that a N -methyl-D-aspartate receptors (NMDAR) hypofunction in the hippocampal dentate gyrus may partly contribute to cognitive impairments in FXS. Since activation of NMDAR plays an important role in dendritic arborization during neuronal development, we examined whether deficits in NMDAR function are associated with alterations in dendritic complexity in the hippocampal dentate region...
2018: Frontiers in Molecular Neuroscience
Iris Wever, Lars von Oerthel, Cindy M R J Wagemans, Marten P Smidt
Over the last decade several components have been identified to be differentially expressed in subsets of mesodiencephalic dopaminergic (mdDA) neurons. These differences in molecular profile have been implied to be involved in the selective degeneration of the SNc neurons in Parkinson's disease. The emergence and maintenance of individual subsets is dependent on different transcriptional programs already present during development. In addition to the influence of transcription factors, recent studies have led to the hypothesis that modifications of histones might also influence the developmental program of neurons...
2018: Frontiers in Molecular Neuroscience
Grit Bornschein, Hartmut Schmidt
Ca2+ concentrations drop rapidly over a distance of a few tens of nanometers from an open voltage-gated Ca2+ channel (Cav ), thereby, generating a spatially steep and temporally short-lived Ca2+ gradient that triggers exocytosis of a neurotransmitter filled synaptic vesicle. These non-steady state conditions make the Ca2+ -binding kinetics of the Ca2+ sensors for release and their spatial coupling to the Cav s important parameters of synaptic efficacy. In the mammalian central nervous system, the main release sensors linking action potential mediated Ca2+ influx to synchronous release are Synaptotagmin (Syt) 1 and 2...
2018: Frontiers in Molecular Neuroscience
Chanté Muller, Paula Morales, Patricia H Reggio
Transient receptor potential (TRP) channels are a group of membrane proteins involved in the transduction of a plethora of chemical and physical stimuli. These channels modulate ion entry, mediating a variety of neural signaling processes implicated in the sensation of temperature, pressure, and pH, as well as smell, taste, vision, and pain perception. Many diseases involve TRP channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders. In the pursuit of new treatments for these disorders, it was discovered that cannabinoids can modulate a certain subset of TRP channels...
2018: Frontiers in Molecular Neuroscience
Chuan Qin, Chang-Bin Liu, De-Gang Yang, Feng Gao, Xin Zhang, Chao Zhang, Liang-Jie Du, Ming-Liang Yang, Jian-Jun Li
Spinal cord injury (SCI) is mostly caused by trauma. As primary mechanical injury is unavoidable in SCI, a focus on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising treatments for SCI patients. Circular RNAs (circRNAs) are associated with various diseases. Nevertheless, studies to date have not yet determined the functional roles of circRNAs in traumatic SCI. We examined circRNA expression profiles in the contused spinal cords of rats using microarray and quantitative reverse transcription-PCR (qRT-PCR) then predict their potential roles in post-SCI pathophysiology with bioinformatics...
2018: Frontiers in Molecular Neuroscience
A Ayanna Wade, Kenneth Lim, Rinaldo Catta-Preta, Alex S Nord
The packaging of DNA into chromatin determines the transcriptional potential of cells and is central to eukaryotic gene regulation. Case sequencing studies have revealed mutations to proteins that regulate chromatin state, known as chromatin remodeling factors, with causal roles in neurodevelopmental disorders. Chromodomain helicase DNA binding protein 8 ( CHD8 ) encodes a chromatin remodeling factor with among the highest de novo loss-of-function mutation rates in patients with autism spectrum disorder (ASD)...
2018: Frontiers in Molecular Neuroscience
Xin-Yi Chen, Yi-Feng Du, Lei Chen
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits and neuronal loss. Deposition of beta-amyloid peptide (Aβ) causes neurotoxicity through the formation of plaques in brains of Alzheimer's disease. Numerous studies have indicated that the neuropeptides including ghrelin, neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y, substance P and orexin are closely related to the pathophysiology of Alzheimer's disease. The levels of neuropeptides and their receptors change in Alzheimer's disease...
2018: Frontiers in Molecular Neuroscience
Hideki Takago, Tomoko Oshima-Takago, Tobias Moser
Sound encoding relies on Ca2+ -mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C2 domain protein, is proposed to regulate Ca2+ -triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution...
2018: Frontiers in Molecular Neuroscience
Laura Orio, Francisco Alen, Francisco Javier Pavón, Antonia Serrano, Borja García-Bueno
Neuroinflammation is a complex process involved in the physiopathology of many central nervous system diseases, including addiction. Alcohol abuse is characterized by induction of peripheral inflammation and neuroinflammation, which hallmark is the activation of innate immunity toll-like receptors 4 (TLR4). In the last years, lipid transmitters have generated attention as modulators of parts of the addictive process. Specifically, the bioactive lipid oleoylethanolamide (OEA), which is an endogenous acylethanolamide, has shown a beneficial profile for alcohol abuse...
2018: Frontiers in Molecular Neuroscience
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