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Ana E Carvajal, María D Vázquez-Carretero, Pablo García-Miranda, María J Peral, María L Calonge, Anunciación A Ilundain
Reelin is an extracellular matrix protein first known for its key role in neuronal migration. Studies in rodent small intestine suggested that reelin protects the organism from intestinal pathology. Here we determined in mice colon, by real time-PCR and immunological assays, the expression of the reelin signalling system; its response to dextran sulphate sodium (DSS) and the response of wild-type and reeler mice to DSS. DNA methylation was determined by bisulfite modification and sequencing of genomic DNA. In the colon mucosa reelin expression is restricted to the myofibroblasts, whereas both epithelial cells and myofibroblasts express reelin receptors (ApoER2 and VLDLR) and its effector protein Dab1...
November 30, 2016: Biochimica et Biophysica Acta
Ayman Alzu'bi, Susan Lindsay, Janet Kerwin, Shi Jie Looi, Fareha Khalil, Gavin J Clowry
The extent of similarities and differences between cortical GABAergic interneuron generation in rodent and primate telencephalon remains contentious. We examined expression of three interneuron precursor transcription factors, alongside other markers, using immunohistochemistry on 8-12 post-conceptional weeks (PCW) human telencephalon sections. NKX2.1, OLIG2, and COUP-TFII expression occupied distinct (although overlapping) neurogenic domains which extended into the cortex and revealed three CGE compartments: lateral, medial, and ventral...
November 30, 2016: Brain Structure & Function
Joanna Yeung, Thomas J Ha, Douglas J Swanson, Dan Goldowitz
UNLABELLED: Pax6 is a prominent gene in brain development. The deletion of Pax6 results in devastated development of eye, olfactory bulb, and cortex. However, it has been reported that the Pax6-null Sey cerebellum only has minor defects involving granule cells despite Pax6 being expressed throughout cerebellar development. The present work has uncovered a requirement of Pax6 in the development of all rhombic lip (RL) lineages. A significant downregulation of Tbr1 and Tbr2 expression is found in the Sey cerebellum, these are cell-specific markers of cerebellar nuclear (CN) neurons and unipolar brush cells (UBCs), respectively...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ming-Wei Chao, Chie-Pein Chen, Yu-Hsiu Yang, Yu-Chen Chuang, Tzu-Yun Chu, Chia-Yi Tseng
Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats...
2016: Scientific Reports
Nissrine Ballout, Isabelle Frappé, Sophie Péron, Mohamed Jaber, Kazem Zibara, Afsaneh Gaillard
Injury to the human central nervous system can lead to devastating consequences due to its poor ability to self-repair. Neural transplantation aimed at replacing lost neurons and restore functional circuitry has proven to be a promising therapeutical avenue. We previously reported in adult rodent animal models with cortical lesions that grafted fetal cortical neurons could effectively re-establish specific patterns of projections and synapses. The current study was designed to provide a detailed characterization of the spatio-temporal in vivo development of fetal cortical transplanted cells within the lesioned adult motor cortex and their corresponding axonal projections...
2016: Frontiers in Neural Circuits
Martin Raasch, Knut Rennert, Tobias Jahn, Claudia Gärtner, Gilbert Schönfelder, Otmar Huber, Andrea E M Seiler, Alexander S Mosig
The development of therapeutic substances to treat diseases of the central nervous system is hampered by the tightness and selectivity of the blood-brain barrier. Moreover, testing of potential drugs is time-consuming and cost-intensive. Here, we established a new microfluidically supported, biochip-based model of the brain endothelial barrier in combination with brain cortical spheroids suitable to detect effects of neuroinflammation upon disruption of the endothelial layer in response to inflammatory signals...
July 2016: Biomicrofluidics
Zsófia Richter, József Janszky, György Sétáló, Réka Horváth, Zsolt Horváth, Tamás Dóczi, László Seress, Hajnalka Ábrahám
The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments...
October 1, 2016: Neuroscience
Cong Sui, Ezekiel Mecha, Charles Oa Omwandho, Anna Starzinski-Powitz, Angelika Stammler, Hans-Rudolf Tinneberg, Lutz Konrad
In the endometrium transforming growth factor-betas (TGF-βs) are involved mainly in menstruation and endometriosis. After binding of the ligands to the high-affinity receptors, TGF-β receptors (TBR1 and TBR2), TGF-βs activate Smad signaling to modulate gene expression and cellular functions. However, recently also Smad-independent pathways have been studied in more details. To evaluate both pathways, we have analyzed TGF-β signaling in human endometrial and endometriotic cells. Although endometrial and endometriotic cells secrete TGF-β1, secretion by stromal cells was higher compared to epithelial cells...
2016: American Journal of Translational Research
James H Notwell, Whitney E Heavner, Siavash Fazel Darbandi, Sol Katzman, William L McKenna, Christian F Ortiz-Londono, David Tastad, Matthew J Eckler, John L R Rubenstein, Susan K McConnell, Bin Chen, Gill Bejerano
Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation...
August 2016: Genome Research
Angelika Mühlebner, Anand M Iyer, Jackelien van Scheppingen, Jasper J Anink, Floor E Jansen, Tim J Veersema, Kees P Braun, Wim G M Spliet, Wim van Hecke, Figen Söylemezoğlu, Martha Feucht, Pavel Krsek, Josef Zamecnik, Christian G Bien, Tilman Polster, Roland Coras, Ingmar Blümcke, Eleonora Aronica
BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disorder that results from mutations in the TSC1 or TSC2 genes, leading to constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway. Cortical tubers represent typical lesions of the central nervous system (CNS) in TSC. The pattern of cortical layering disruption observed in brain tissue of TSC patients is not yet fully understood, and little is known about the origin and phenotype of individual abnormal cell types recognized in tubers...
2016: Journal of Neurodevelopmental Disorders
Youichi Uda, Shuai Xu, Takafumi Matsumura, Yoshinori Takei
Neural stem cells (NSCs) produce all neuronal subtypes involved in the nervous system. The mechanism regulating their subtype selection is not fully understood. We found that the expression of the nucleotide receptor P2Y4 was transiently augmented in the course of neuronal differentiation of mouse embryonic stem cells (ESCs), which was after loss of pluripotency but prior to terminal differentiation of neurons. The activation of P2Y4 in the differentiating ESCs resulted in an increased proportion of neurons expressing vesicular glutamate transporter (vGluT), a marker of glutamatergic subtype...
April 12, 2016: Stem Cell Reports
Lauren F Harkin, Dianne Gerrelli, Diana C Gold Diaz, Chloe Santos, Ayman Alzu'bi, Caroline A Austin, Gavin J Clowry
TOP2A and TOP2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post-conceptional weeks. TOP2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences (GE), including the ventricular zone and subventricular zone (SVZ) closely matching expression of the proliferation marker KI67...
March 2016: Journal of Anatomy
Tzyy-Nan Huang, Yi-Ping Hsueh
T-brain-1 (TBR1) is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1 (-∕-) mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala, and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1. Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs)...
2015: Frontiers in Neuroscience
Akihito, Fumihito Akishinonomiya, Yuji Ikeda, Masahiro Aizawa, So Nakagawa, Yumi Umehara, Takahiro Yonezawa, Shuhei Mano, Masami Hasegawa, Tetsuji Nakabo, Takashi Gojobori
To understand how geographical differentiation of gobioid fish species led to speciation, two populations of the Pacific Ocean and the Sea of Japan for each of the two gobioid species, Pterogobius elapoides and Pterogobius zonoleucus, were studied in both morphological and molecular features. Analyzing mitochondrial genes, Akihito et al. (2008) suggested that P. zonoleucus does not form a monophyletic clade relative to P. elapoides, indicating that "Sea of Japan P. zonoleucus" and P. elapoides form a clade excluding "Pacific P...
February 1, 2016: Gene
C R Easton, C W Dickey, S P Moen, K E Neuzil, Z Barger, T M Anderson, W J Moody, R F Hevner
Cortical development involves the structuring of network features by genetically programmed molecular signaling pathways. Additionally, spontaneous ion channel activity refines neuronal connections. We examine Ca(2+) fluctuations in the first postnatal week of normal mouse neocortex and that expressing knockout of the transcription factor T-brain-1 (Tbr1): a signaling molecule in cortical patterning and differentiation of excitatory neurons. In cortex, glutamatergic neurons express Tbr1 just before the onset of population electrical activity that is accompanied by intracellular Ca(2+) increases...
July 2016: Developmental Neurobiology
Sonia Tehseen, Nusrat Jahan, Muhammad Fiaz Qamar, Marc Desquesnes, Mirza Imran Shahzad, Stijn Deborggraeve, Philippe Büscher
BACKGROUND: Surra, a vector borne disease caused by Trypanosoma (T.) evansi, affects the health, productivity and working capacity of camels. Since clinical signs are not pathognomonic, diagnosis must be confirmed by laboratory methods. This is a first study on the prevalence of surra in Cholistan Desert, Pakistan using a broad variety of diagnostic tests thereby emphasizing it as a risk for the dromedaries of Pakistan. METHODS: In a cross sectional study, 1005 dromedary camels from three districts in the Cholistan Desert were sampled to assess the prevalence of trypanosomosis due to T...
August 12, 2015: Parasites & Vectors
Federico Luzzati
The neocortex is unique to mammals and its evolutionary origin is still highly debated. The neocortex is generated by the dorsal pallium ventricular zone, a germinative domain that in reptiles give rise to the dorsal cortex. Whether this latter allocortical structure contains homologs of all neocortical cell types it is unclear. Recently we described a population of DCX+/Tbr1+ cells that is specifically associated with the layer II of higher order areas of both the neocortex and of the more evolutionary conserved piriform cortex...
2015: Frontiers in Neuroscience
Eun-Jae Lee, Hyejin Lee, Tzyy-Nan Huang, Changuk Chung, Wangyong Shin, Kyungdeok Kim, Jae-Young Koh, Yi-Ping Hsueh, Eunjoon Kim
Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs have received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, but evidence for a strong association and linking mechanism is largely lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues social interaction in two independent mouse models of ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation induced by clioquinol (a Zn chelator and ionophore) improves social interaction...
2015: Nature Communications
José Cánovas, F Andrés Berndt, Hugo Sepúlveda, Rodrigo Aguilar, Felipe A Veloso, Martín Montecino, Carlos Oliva, Juan C Maass, Jimena Sierralta, Manuel Kukuljan
The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate...
May 13, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sara Cipriani, Jeannette Nardelli, Catherine Verney, Anne-Lise Delezoide, Fabien Guimiot, Pierre Gressens, Homa Adle-Biassette
The molecular mechanisms underlying the formation of hippocampus are unknown in humans. To improve our knowledge of molecules that potentially regulate pyramidal neurogenesis and layering in various hippocampal fields, we investigated the expression of progenitor markers and cell fate molecules from gestational week (GW) 9 to GW 20. At GW 9, the progenitor cell compartment of the hippocampal formation mainly consisted of PAX6(+) cells in the ventricular zone. Between GW 9 and 11, a second germinal area, the subventricular zone (SVZ), was formed, as shown by TBR2 labeling...
March 2016: Cerebral Cortex
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