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Julia N Bailey, Laurence de Nijs, Dongsheng Bai, Toshimitsu Suzuki, Hiroyuki Miyamoto, Miyabi Tanaka, Christopher Patterson, Yu-Chen Lin, Marco T Medina, María E Alonso, José M Serratosa, Reyna M Durón, Viet H Nguyen, Jenny E Wight, Iris E Martínez-Juárez, Adriana Ochoa, Aurelio Jara-Prado, Laura Guilhoto, Yolly Molina, Elsa M Yacubian, Minerva López-Ruiz, Yushi Inoue, Sunao Kaneko, Shinichi Hirose, Makiko Osawa, Hirokazu Oguni, Shinji Fujimoto, Thierry M Grisar, John M Stern, Kazuhiro Yamakawa, Bernard Lakaye, Antonio V Delgado-Escueta
BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK)...
March 15, 2018: New England Journal of Medicine
A Raček, K Beňová, P Arnoul, M Závodská, A Angelidis, V Cigánková, V Šimaiová, E Račeková
Processes of adult neurogenesis can be influenced by environmental factors. Here, we investigated the effect of microwave radiation (MWR) on proliferation and cell dying in the rat rostral migratory stream (RMS) - a migration route for the neuroblasts of the subventricular zone. Adult and juvenile (two weeks old) rats were exposed to a pulsed-wave MWR at the frequency of 2.45 GHz for 3 h daily during 3 weeks. Adult rats were divided into two groups: without survival and with two weeks survival after irradiation...
March 12, 2018: Physiological Research
Chun-Ho Park, Nozomi Shiwa, Kazunori Kimitsuki, Takehito Kakizaki, Daisaku Watanabe
This case report describes a congenital ganglioneuroblastoma in a 38-day-old male Japanese Black calf. The cervical multinodular mass was present at birth and grew rapidly. The cut surface was pale gray-to-yellow and had a gelatinous appearance. Hemorrhagic cysts of various sizes were observed in the nodule. Histologically, the mass contained clusters of neuroblastic cells, ganglionic cells, and Schwann-like cells. Immunohistochemically, the ganglionic cells showed strong positivity for neuron-specific enolase, neurofilament, synaptophysin, and chromogranin A, whereas the Schwann-like cells strongly expressed S-100, glial fibrillary acidic protein, and vimentin...
March 9, 2018: Journal of Veterinary Medical Science
Laure-Estelle Cassagnes, Monivan Chhour, Pierre Perio, Jan Sudor, Régis Gayon, Gilles Ferry, Jean A Boutin, Françoise Nepveu, Karine Reybier
There is increasing evidence that oxidative stress is involved in the etiology and pathogenesis of neurodegenerative disorders. Overproduction of reactive oxygen species (ROS) is due in part to the reactivity of catecholamines, such as dopamine, adrenaline, and noradrenaline. These molecules are rapidly converted, chemically or enzymatically, into catechol-quinone and then into highly deleterious semiquinone radicals after 1-electron reduction in cells. Notably, the overexpression of dihydronicotinamide riboside:quinone oxidoreductase (QR2) in Chinese hamster ovary (CHO) cells increases the production of ROS, mainly superoxide radicals, when it is exposed to exogenous catechol-quinones (e...
March 8, 2018: Free Radical Biology & Medicine
Yongping Chai, Zhiwen Zhu, Guangshuo Ou
During C. elegans larval development, the Q neuroblasts produce their lineage by three rounds of divisions along with continuous cell migrations. Their neuronal progeny is dispersed from the pharynx to the anus. This in vivo system to study cell migration is appealing for several reasons. The lineage development is stereotyped; functional analysis and genomic screens are rendered easy and powerful thanks to powerful tools; transgenic manipulations and genome engineering are efficient and can be conveniently combined with live-cell imaging...
2018: Methods in Molecular Biology
Cristina Molnar, Beatriz Estrada, Jose F de Celis
Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells...
March 9, 2018: Genes, Brain, and Behavior
Simone Culurgioni, Sara Mari, Paola Bonetti, Sara Gallini, Greta Bonetto, Martha Brennich, Adam Round, Francesco Nicassio, Marina Mapelli
Asymmetric cell divisions balance stem cell proliferation and differentiation to sustain tissue morphogenesis and homeostasis. During asymmetric divisions, fate determinants and niche contacts segregate unequally between daughters, but little is known on how this is achieved mechanistically. In Drosophila neuroblasts and murine mammary stem cells, the association of the spindle orientation protein LGN with the stem cell adaptor Inscuteable has been connected to asymmetry. Here we report the crystal structure of Drosophila LGN in complex with the asymmetric domain of Inscuteable, which reveals a tetrameric arrangement of intertwined molecules...
March 9, 2018: Nature Communications
Joon Ha Park, Bich Na Shin, Ji Hyeon Ahn, Jeong Hwi Cho, Tae-Kyeong Lee, Jae-Chul Lee, Yong Hwan Jeon, Il Jun Kang, Ki-Yeon Yoo, In Koo Hwang, Choong Hyun Lee, Yoo Hun Noh, Sung-Su Kim, Moo-Ho Won, Jong Dai Kim
Background: Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. Methods: A total of 39 male ICR mice (12 weeks old) were randomly assigned to vehicle-treated and 100 and 200 mg/kg G...
March 20, 2018: Chinese Medical Journal
Thomas V Wuttke, Foivos Markopoulos, Hari Padmanabhan, Aaron P Wheeler, Venkatesh N Murthy, Jeffrey D Macklis
Repair of complex CNS circuitry requires newly incorporated neurons to become appropriately, functionally integrated. One approach is to direct differentiation of endogenous progenitors in situ, or ex vivo followed by transplantation. Prior studies find that newly incorporated neurons can establish long-distance axon projections, form synapses and functionally integrate in evolutionarily old hypothalamic energy-balance circuitry. We now demonstrate that postnatal neocortical connectivity can be reconstituted with point-to-point precision, including cellular integration of specific, molecularly identified projection neuron subtypes into correct positions, combined with development of appropriate long-distance projections and synapses...
March 5, 2018: Nature Neuroscience
Paul W Hook, Sarah A McClymont, Gabrielle H Cannon, William D Law, A Jennifer Morton, Loyal A Goff, Andrew S McCallion
Genetic variation modulating risk of sporadic Parkinson disease (PD) has been primarily explored through genome-wide association studies (GWASs). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra (SN) DA neurons...
March 1, 2018: American Journal of Human Genetics
Makoto I Kanai, Myung-Jun Kim, Takuya Akiyama, Masahiko Takemura, Kristi Wharton, Michael B O'Connor, Hiroshi Nakato
Despite the importance of precisely regulating stem cell division, the molecular basis for this control is still elusive. Here, we show that surface glia in the developing Drosophila brain play essential roles in regulating the proliferation of neural stem cells, neuroblasts (NBs). We found that two classes of extracellular factors, Dally-like (Dlp), a heparan sulfate proteoglycan, and Glass bottom boat (Gbb), a BMP homologue, are required for proper NB proliferation. Interestingly, Dlp expressed in perineural glia (PG), the most outer layer of the surface glia, is responsible for NB proliferation...
February 27, 2018: Scientific Reports
Chwee Tat Koe, Ye Sing Tan, Max Lönnfors, Seong Kwon Hur, Christine Siok Lan Low, Yingjie Zhang, Pakorn Kanchanawong, Vytas A Bankaitis, Hongyan Wang
A central feature of most stem cells is the ability to self-renew and undergo differentiation via asymmetric division. However, during asymmetric division the role of phosphatidylinositol (PI) lipids and their regulators is not well established. Here, we show that the sole type I PI transfer protein, Vibrator, controls asymmetric division of Drosophila neural stem cells (NSCs) by physically anchoring myosin II regulatory light chain, Sqh, to the NSC cortex. Depletion of vib or disruption of its lipid binding and transfer activities disrupts NSC polarity...
February 27, 2018: ELife
Aditi Falnikar, Jarred Stratton, Ruihe Lin, Carrie E Andrews, Ashley Tyburski, Victoria A Trovillion, Chelsea Gottschalk, Biswarup Ghosh, Lorraine Iacovitti, Melanie B Elliott, Angelo C Lepore
Populations of neural stem cells (NSCs) reside in a number of defined niches in the adult CNS where they continually give rise to mature cell types throughout life, including newly-born neurons. In addition to prototypical niches of the subventricular zone and subgranular zone of the hippocampal dentate gyrus, novel stem cell niches that are also neurogenic have recently been identified in multiple midline structures, including circumventricular organs (CVOs) of the brain. These resident NSCs may have the potential for reparative processes in pathologies such as traumatic spinal cord injury (SCI) and traumatic brain injury (TBI)...
February 22, 2018: Journal of Neurotrauma
Jannis Gundelach, Michael Koch
Clinical treatment of structural brain damage today is largely limited to symptomatic approaches and the avoidance of secondary injury. However, neuronal precursor cells are constantly produced within specified regions of the mammalian brain throughout life. Here we evaluate the potential of the known chemoattractive properties of the glycoprotein laminin on neuroblasts to relocate the cells into damaged brain areas. Injection of a thin laminin tract, leading from the rostral migratory stream to an excitotoxic lesion within the medial prefrontal cortex of rats, enabled neuroblasts to migrate away from their physiological route towards the olfactory bulb into the lesion site...
February 21, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Zelin Shan, Yuting Tu, Ying Yang, Ziheng Liu, Menglong Zeng, Huisha Xu, Jiafu Long, Mingjie Zhang, Yu Cai, Wenyu Wen
Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode...
February 21, 2018: Nature Communications
Binglong Zhang, Kosei Sato, Daisuke Yamamoto
Some mAL neurons in the male brain form the ipsilateral neurite (ILN[+]) in a manner dependent on FruBM, a male-specific transcription factor. FruBM represses robo1 transcription, allowing the ILN to form. We found that the proportion of ILN[+]-mALs in all observed single cell clones dropped from ∼90% to ∼30% by changing the heat-shock timing for clone induction from 4-5 days after egg laying (AEL) to 6-7 days AEL, suggesting that the ILN[+]-mALs are produced predominantly by young neuroblasts. Upon EcR-A knockdown, ILN[+]-mALs were produced at a high rate (∼60%), even when heat shocked at 6-7 days AEL, yet EcR-B1 knockdown reduced the proportion of ILN[+]-mALs to ∼30%...
February 20, 2018: Biology Open
Lennard J M Dekker, Lona Zeneyedpour, Sandor Snoeijers, Jos Joore, Sieger Leenstra, Theo M Luider
We show that parallel reaction monitoring (PRM) can be used for exact quantification of phosphorylation ratios of proteins using stable isotope labelled peptides. We have compared two different PRM approaches on a digest of a U87 cell culture, namely direct-PRM (tryptic digest measured by PRM without any further sample preparation) and TiO2-PRM (tryptic digest enriched with TiO2 cartridges, followed by PRM measurement); these approaches are compared for the following phosphorylation sites: Neuroblast differentiation-associated protein (AHNAK S5480-p), Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D T337-p) and Epidermal growth factor receptor (EGFR S1166-p)...
February 19, 2018: Journal of Proteome Research
Yanling Zhu, Yang Qiu, Mengjia Chen, Yi Zhang, Li Cao, Zhida Su, Yimin Yuan, Aijun Huang, Yinyan Pu, Cheng He
The neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein, has been extensively studied as a heme scavenger at the systemic level. However, little is known about its function in the central nervous system, especially in neurogenesis. In the present study, we demonstrate that deletion of hemopexin leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was observed in Dcx+ cells...
February 15, 2018: Cell Death & Disease
Aidan M Sokolov, Caitlin M Seluzicki, Mary C Morton, David M Feliciano
Ras homology enriched in brain (Rheb) is a GTPase that activates the protein kinase mammalian Target of Rapamycin (mTOR). Rheb mutations cause intellectual delay and megalencephaly. mTOR hyperactivation causes a constellation of neurodevelopmental disorders called "mTOR-opathies" that are frequently accompanied by hyperexcitable cortical malformations. Cortical malformations within the anterior cingulate cortex (ACC) and somatosensory cortex (SSC) frequently colocalize with hyperexcitability. Although Rheb and mTOR are implicated in the formation of cortical lesions, seizure activity, and defects in neuronal migration, the contribution of Rheb to changes in neuron size and dendrite morphology is not well established...
February 12, 2018: Neuroscience Letters
Yusuke Hara, Tatsuya Sudo, Yu Togane, Hiromi Akagawa, Hidenobu Tsujimura
Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development...
February 12, 2018: Developmental Biology
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