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https://www.readbyqxmd.com/read/29150182/mature-hippocampal-neurons-require-lis1-for-synaptic-integrity-implications-for-cognition
#1
Anamaria Sudarov, Xin-Jun Zhang, Leighton Braunstein, Eve LoCastro, Shawn Singh, Yu Taniguchi, Ashish Raj, Song-Hai Shi, Holly Moore, M Elizabeth Ross
BACKGROUND: Platelet-activating factor acetylhydrolase 1B1 (LIS1), a critical mediator of neuronal migration in developing brain, is expressed throughout life. However, relatively little is known about LIS1 function in the mature brain. We previously demonstrated that LIS1 involvement in the formation and turnover of synaptic protrusions and synapses of young brain after neuronal migration is complete. Here we examine the requirement for LIS1 to maintain hippocampal circuit function in adulthood...
September 23, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#2
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29144974/double-nanodomain-coupling-of-calcium-channels-ryanodine-receptors-and-bk-channels-controls-the-generation-of-burst-firing
#3
Tomohiko Irie, Laurence O Trussell
Action potentials clustered into high-frequency bursts play distinct roles in neural computations. However, little is known about ionic currents that control the duration and probability of these bursts. We found that, in cartwheel inhibitory interneurons of the dorsal cochlear nucleus, the likelihood of bursts and the interval between their spikelets were controlled by Ca(2+) acting across two nanodomains, one between plasma membrane P/Q Ca(2+) channels and endoplasmic reticulum (ER) ryanodine receptors and another between ryanodine receptors and large-conductance, voltage- and Ca(2+)-activated K(+) (BK) channels...
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29138490/bidirectional-modulation-of-hippocampal-synaptic-plasticity-by-dopaminergic-d4-receptors-in-the-ca1-area-of-hippocampus
#4
Sheeja Navakkode, Katherine C M Chew, Sabrina Jia Ning Tay, Qingshu Lin, Thomas Behnisch, Tuck Wah Soong
Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137974/effects-and-mechanisms-of-matrix-metalloproteinase2-on-neural-differentiation-of-induced-pluripotent-stem-cells
#5
Tao Shu, Chang Liu, Mao Pang, Juan Wang, Bin Liu, Wei Zhou, Xuan Wang, Tao Wu, Qiyou Wang, Limin Rong
Induced pluripotent stem cells (iPSCs) possess the potential to differentiate into neural lineage cells. Matrix metalloproteinase 2 (MMP2), an endopeptidase in the extracellular matrix, has been shown to protect neural cells from injury. However, the mechanisms and effects of MMP2 on neural differentiation of iPSCs remain poorly understood. Here, we demonstrated a role for MMP2 in the differentiation of iPSCs to neurons via the AKT pathway. Treatment of iPSCs with MMP2 promoted their proliferation and differentiation into neural stem cells (NSCs), and then into neurons...
November 11, 2017: Brain Research
https://www.readbyqxmd.com/read/29137400/downregulation-of-the-sonic-hedgehog-gli-pathway-transcriptional-target-neogenin-1-is-associated-with-basal-cell-carcinoma-aggressiveness
#6
Bárbara S Casas, Christelle Adolphe, Pablo Lois, Nelson Navarrete, Natalia Solís, Eva Bustamante, Patricio Gac, Patricio Cabané, Ivan Gallegos, Brandon J Wainwright, Verónica Palma
Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#7
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29136107/contextual-fear-extinction-induces-hippocampal-metaplasticity-mediated-by-metabotropic-glutamate-receptor-5
#8
Branden J Stansley, Nicole M Fisher, Rocco G Gogliotti, Craig W Lindsley, P Jeffrey Conn, Colleen M Niswender
Dysregulated fear memory can lead to a broad spectrum of anxiety disorders. The brain systems underlying fear memory are manifold, with the hippocampus being prominently involved by housing fear-related spatial memories as engrams, which are created and stored through neural changes such as synaptic plasticity. Although metabotropic glutamate (mGlu) receptors contribute significantly to both fear behavior and hippocampal synaptic plasticity, the relationship between these two phenomena has not been fully elucidated...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29134430/modern-drug-design-the-implication-of-using-artificial-neuronal-networks-and-multiple-molecular-dynamic-simulations
#9
Oleksandr Yakovenko, Steven J M Jones
We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource ( https://drugdesigndata.org/ ). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein...
November 13, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29134414/pax3-promotes-cell-migration-and-cxcr4-gene-expression-in-neural-crest-cells
#10
Man Xu, Yongle Li, Jinfeng Du, Hengrong Lin, Sixian Cao, Zuming Mao, Ronghua Wu, Mei Liu, Yan Liu, Qiyou Yin
Neural crest (NC) cells are a multipotent cell population with powerful migration ability during development. C-X-C chemokine receptor type 4 (CXCR4) is a chemokine receptor implicated to mediate NC migration in various species, whereas the underlying mechanism is not well documented yet. PAX3 is a critical transcription factor for the formation of neural crest and the migration and differentiation of NCs. In this study, we retrieved a potential PAX3 binding element in the promoter of the CXCR4 gene, and we further found that PAX3 could promote the expression of CXCR4 and facilitate the migration of NCs...
November 13, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29133952/engaging-homeostatic-plasticity-to-treat-depression
#11
E R Workman, F Niere, K F Raab-Graham
Major depressive disorder (MDD) is a complex and heterogeneous mood disorder, making it difficult to develop a generalized, pharmacological therapy that is effective for all who suffer from MDD. Through the fortuitous discovery of N-methyl-D-aspartate receptor (NMDAR) antagonists as effective antidepressants, we have gained key insights into how antidepressant effects can be produced at the circuit and molecular levels. NMDAR antagonists act as rapid-acting antidepressants such that relief from depressive symptoms occurs within hours of a single injection...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133907/a-primacy-code-for-odor-identity
#12
Christopher D Wilson, Gabriela O Serrano, Alexei A Koulakov, Dmitry Rinberg
Humans can identify visual objects independently of view angle and lighting, words independently of volume and pitch, and smells independently of concentration. The computational principles underlying invariant object recognition remain mostly unknown. Here we propose that, in olfaction, a small and relatively stable set comprised of the earliest activated receptors forms a code for concentration-invariant odor identity. One prediction of this "primacy coding" scheme is that decisions based on odor identity can be made solely using early odor-evoked neural activity...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133394/role-of-estrogen-receptor-beta-in-neural-differentiation-of-mouse-embryonic-stem-cells
#13
Mukesh K Varshney, José Inzunza, Diana Lupu, Vaidheeswaran Ganapathy, Per Antonson, Joëlle Rüegg, Ivan Nalvarte, Jan-Åke Gustafsson
The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain. To examine whether ERβ influences differentiation of mouse embryonic stem cells (mESC) into neural lineages, we compared control and ERβ knockout (BERKO) mESCs at defined stages of neural development and examined the effects of an ERβ-selective ligand (LY3201) with a combination of global and targeted gene-expression profiling and the expression of key pluripotency markers...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29132949/redefining-neuroendocrinology-epigenetics-of-brain-body-communication-over-the-life-course
#14
REVIEW
Bruce S McEwen
The brain is the central organ of stress and adaptation to stress that perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor, and it does so somewhat differently in males and females. The expression of steroid hormone receptors throughout the brain has broadened the definition of 'neuroendocrinology' to include the reciprocal communication between the entire brain and body via hormonal and neural pathways. Mediated in part via systemic hormonal influences, the adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover...
November 10, 2017: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/29132503/gyrification-of-the-cerebral-cortex-requires-fgf-signaling-in-the-mammalian-brain
#15
Naoyuki Matsumoto, Yohei Shinmyo, Yoshie Ichikawa, Hiroshi Kawasaki
Although it has been believed that the evolution of cortical folds was a milestone, allowing for an increase in the number of neurons in the cerebral cortex, the mechanisms underlying the formation of cortical folds are largely unknown. Here we show regional differences in the expression of fibroblast growth factor receptors (FGFRs) in the developing cerebral cortex of ferrets even before cortical folds are formed. By taking the advantage of our in utero electroporation technique for ferrets, we found that cortical folding was impaired in the ferret cerebral cortex when FGF signaling was inhibited...
November 14, 2017: ELife
https://www.readbyqxmd.com/read/29132374/yeast-interfering-rna-larvicides-targeting-neural-genes-induce-high-rates-of-anopheles-larval-mortality
#16
Keshava Mysore, Limb K Hapairai, Longhua Sun, Elizabeth I Harper, Yingying Chen, Kathleen K Eggleson, Jacob S Realey, Nicholas D Scheel, David W Severson, Na Wei, Molly Duman-Scheel
BACKGROUND: Although larviciding can reduce the number of outdoor biting malaria vector mosquitoes, which may help to prevent residual malaria transmission, the current larvicide repertoire is faced with great challenges to sustainability. The identification of new effective, economical, and biorational larvicides could facilitate maintenance and expansion of the practice of larviciding in integrated malaria vector mosquito control programmes. Interfering RNA molecules represent a novel class of larvicides with untapped potential for sustainable mosquito control...
November 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29132133/endomorphins-promising-endogenous-opioid-peptides-for-the-development-of-novel-analgesics
#17
Zheng-Hui Gu, Bo Wang, Zhen-Zhen Kou, Yang Bai, Tao Chen, Yu-Lin Dong, Hui Li, Yun-Qing Li
Endomorphin-1 (EM1) and endomorphin-2 (EM2) are two endogenous ligands that belong to the opioid peptide family and have the highest affinity and selectivity for the µ-opioid receptor (MOR). The neuroanatomical distribution, ultrastructural features and neural circuitry of EM-containing neuronal structures have been morphologically demonstrated. In addition, the modulation effects of the EMs in different areas reflect their potential endogenous roles in many major physiological processes, including their remarkable roles in the transmission and modulation of noxious information...
November 13, 2017: Neuro-Signals
https://www.readbyqxmd.com/read/29129686/naive-like-esrrb-ipscs-with-the-capacity-for-rapid-neural-differentiation
#18
Fumihiko Kisa, Seiji Shiozawa, Keisuke Oda, Sho Yoshimatsu, Mari Nakamura, Ikuko Koya, Kenji Kawai, Sadafumi Suzuki, Hideyuki Okano
Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs), i.e., a naive state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naive-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naive state through the transgenic expression of several reprogramming factors...
November 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129316/functional-consequences-of-chrna7-copy-number-alterations-in-induced-pluripotent-stem-cells-and-neural-progenitor-cells
#19
Madelyn A Gillentine, Jiani Yin, Aleksandar Bajic, Ping Zhang, Steven Cummock, Jean J Kim, Christian P Schaaf
Copy-number variants (CNVs) of chromosome 15q13.3 manifest clinically as neuropsychiatric disorders with variable expressivity. CHRNA7, encoding for the α7 nicotinic acetylcholine receptor (nAChR), has been suggested as a candidate gene for the phenotypes observed. Here, we used induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) derived from individuals with heterozygous 15q13.3 deletions and heterozygous 15q13.3 duplications to investigate the CHRNA7-dependent molecular consequences of the respective CNVs...
November 4, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29128319/a-proteomic-investigation-into-mechanisms-underpinning-corticosteroid-effects-on-neural-stem-cells
#20
Rawaa S Al-Mayyahi, Luke D Sterio, Joanne B Connolly, Christopher F Adams, Wa'il A Al-Tumah, Jon Sen, Richard D Emes, Sarah R Hart, Divya M Chari
Corticosteroids (CSs) are widely used clinically, for example in pediatric respiratory distress syndrome, and immunosuppression to prevent rejection of stem cell transplant populations in neural cell therapy. However, such treatment can be associated with adverse effects such as impaired neurogenesis and myelination, and increased risk of cerebral palsy. There is increasing evidence that CSs can adversely influence key biological properties of neural stem cells (NSCs) but the molecular mechanisms underpinning such effects are largely unknown...
November 8, 2017: Molecular and Cellular Neurosciences
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