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https://www.readbyqxmd.com/read/29780409/beneficial-effects-of-resveratrol-mediated-inhibition-of-the-mtor-pathway-in-spinal-cord-injury
#1
REVIEW
Jingying Zhou, Xue Huo, Benson O A Botchway, Luyao Xu, Xiaofang Meng, Songou Zhang, Xuehong Liu
Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29778488/the-2016-bernard-sachs-lecture-timing-in-morphogenesis-and-genetic-gradients-during-normal-development-and-in-malformations-of-the-nervous-system
#2
REVIEW
Harvey B Sarnat
Nervous system development is quadradimensional. Both normal ontogenesis and developmental malformations are explained in the context of the fourth dimension, timing. Timing of the onset of either the genetic expression of a mutation or an epigenetic event that may be teratogenic is primordial in determining morphogenesis and the forms of malformations with their functional consequences. Multiple genotypes may cause similar phenotypes or a single genotype with different degrees of retained normal genetic expression may result in variable phenotypes...
March 30, 2018: Pediatric Neurology
https://www.readbyqxmd.com/read/29773580/resistin-inhibits-neuronal-autophagy-through-toll-like-receptor-4
#3
Jie Miao, Yacir Benomar, Sarah Al-Rifai, Ghislaine Poizat, Laure Riffault, Delphine Crepin, Mohammed Taouis
Autophagy is as a non-selective degradation pathway induced in energy-deprived cells and in non-starved cells by participating in cellular inflammatory responses mainly through the elimination of injured and aged mitochondria that constitute an important source of reactive oxygen species. We have previously reported that resistin/TLR4 signaling pathway induces inflammation and insulin resistance in neuronal cell. However, the impact of resistin-induced inflammation on neuronal autophagy is unknown. In the present study, we hypothesized that resistin-induced neuroinflammation could be attributed, at least partially, to the impairment of autophagy pathways in neuronal cells...
May 17, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29770442/current-concepts-in-the-neuropathogenesis-of-mucolipidosis-type-iv
#4
REVIEW
Lauren C Boudewyn, Steven U Walkley
Mucolipidosis type IV (MLIV) is an autosomal recessive, lysosomal storage disorder causing progressively severe intellectual disability, motor and speech deficits, retinal degeneration often culminating in blindness, and systemic disease causing a shortened lifespan. MLIV results from mutations in the gene MCOLN1 encoding the transient receptor potential channel mucolipin-1. It is an ultra-rare disease and is currently known to affect just over 100 diagnosed individuals. The last decade has provided a wealth of research focused on understanding the role of the enigmatic mucolipin-1 protein in cell and brain function and how its absence causes disease...
May 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29763645/agmatine-potentiates-neuroprotective-effects-of-subthreshold-concentrations-of-ketamine-via-mtor-s6-kinase-signaling-pathway
#5
Mauren K Tavares, Suellen Dos Reis, Nicolle Platt, Isabella A Heinrich, Ingrid A V Wolin, Rodrigo B Leal, Manuella P Kaster, Ana Lúcia S Rodrigues, Andiara E Freitas
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most robust neurobiological findings in the pathophysiology of major depressive disorder (MDD) over the last 40 years. The persistent increase in glucocorticoids levels induces morphological and anatomical changes in the brain, especially in the hippocampus. Ketamine represents a major advance for the treatment of MDD, however the psychotomimetic effects of this compound limit its widespread use. Agmatine is a neuromodulator that has been shown to be a putative novel and well-tolerated antidepressant/augmenter drug...
May 12, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29761115/depdc5-knockdown-causes-mtor-dependent-motor-hyperactivity-in-zebrafish
#6
Hortense de Calbiac, Adriana Dabacan, Elise Marsan, Hervé Tostivint, Gabrielle Devienne, Saeko Ishida, Eric Leguern, Stéphanie Baulac, Raul C Muresan, Edor Kabashi, Sorana Ciura
Objective: DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Methods: Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29755318/arc-3-utr-splicing-leads-to-dual-and-antagonistic-effects-in-fine-tuning-arc-expression-upon-bdnf-signaling
#7
Chiara Paolantoni, Simona Ricciardi, Veronica De Paolis, Chinenye Okenwa, Caterina Catalanotto, Maria T Ciotti, Antonino Cattaneo, Carlo Cogoni, Corinna Giorgi
Activity-regulated cytoskeletal associated protein (Arc) is an immediate-early gene critically involved in synaptic plasticity and memory consolidation. Arc mRNA is rapidly induced by synaptic activation and a portion is locally translated in dendrites where it modulates synaptic strength. Being an activity-dependent effector of homeostatic balance, regulation of Arc is uniquely tuned to result in short-lived bursts of expression. Cis -Acting elements that control its transitory expression post-transcriptionally reside primarily in Arc mRNA 3' UTR...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29751355/targeting-of-microrna-21-5p-protects-against-seizure-damage-in-a-kainic-acid-induced-status-epilepticus-model-via-pten-mtor
#8
Chongyang Tang, Yunhe Gu, Haiyang Wang, Hongmei Wu, Yu Wang, Yao Meng, Zhibin Han, Yifei Gu, Wei Ma, Zhenfeng Jiang, Yuanyuan Song, Meng Na, Dunyue Lu, Zhiguo Lin
OBJECTIVE: Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acid rat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. METHOD: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis...
May 4, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29749694/trimethylamine-n-oxide-promotes-brain-aging-and-cognitive-impairment-in-mice
#9
Dang Li, Yilang Ke, Rui Zhan, Changjie Liu, Mingming Zhao, Aiping Zeng, Xiaoyun Shi, Liang Ji, Si Cheng, Bing Pan, Lemin Zheng, Huashan Hong
Gut microbiota can influence the aging process and may modulate aging-related changes in cognitive function. Trimethylamine-N-oxide (TMAO), a metabolite of intestinal flora, has been shown to be closely associated with cardiovascular disease and other diseases. However, the relationship between TMAO and aging, especially brain aging, has not been fully elucidated. To explore the relationship between TMAO and brain aging, we analysed the plasma levels of TMAO in both humans and mice and administered exogenous TMAO to 24-week-old senescence-accelerated prone mouse strain 8 (SAMP8) and age-matched senescence-accelerated mouse resistant 1 (SAMR1) mice for 16 weeks...
May 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29740323/the-selective-antagonism-of-adenosine-a-2b-receptors-reduces-the-synaptic-failure-and-neuronal-death-induced-by-oxygen-and-glucose-deprivation-in-rat-ca1-hippocampus-in-vitro
#10
Irene Fusco, Filippo Ugolini, Daniele Lana, Elisabetta Coppi, Ilaria Dettori, Lisa Gaviano, Daniele Nosi, Federica Cherchi, Felicita Pedata, Maria G Giovannini, Anna M Pugliese
Ischemia is a multifactorial pathology characterized by different events evolving in time. Immediately after the ischemic insult, primary brain damage is due to the massive increase of extracellular glutamate. Adenosine in the brain increases dramatically during ischemia in concentrations able to stimulate all its receptors, A1 , A2A , A2B , and A3 . Although adenosine exerts clear neuroprotective effects through A1 receptors during ischemia, the use of selective A1 receptor agonists is hampered by their undesirable peripheral side effects...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29738527/defensive-effect-of-microrna-200b-c-against-amyloid-beta-peptide-induced-toxicity-in-alzheimer-s-disease-models
#11
Sayuri Higaki, Masashi Muramatsu, Akio Matsuda, Kenji Matsumoto, Jun-Ichi Satoh, Makoto Michikawa, Shumpei Niida
MiRNA molecules are important post-transcriptional regulators of gene expression in the brain function. Altered miRNA profiles could represent a defensive response against the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other gene silencing methods, thus enhancing the expression of defensive miRNA could be an effective therapy. However, little is known about the potential of targeting miRNAs for the treatment of AD. Here, we examined the function of the miR-200 family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray analysis of cortical tissue from Tg2576 transgenic mice...
2018: PloS One
https://www.readbyqxmd.com/read/29736615/bdnf-reduces-eef2-phosphorylation-and-enhances-novel-protein-synthesis-in-the-growth-cones-of-dorsal-root-ganglia-neurons
#12
Osamu Hoshi, Ayana Sugizaki, Yuichiro Cho, Nobuyuki Takei
The local translation, which is regulated by extracellular stimuli such as guidance molecules, in growth cones of neurons provides a molecular mechanism for axonal development. In this study, we performed immunocytochemistry together with atomic force microscopy to investigate the localization of ribosomal proteins in the growth cones of rat dorsal root ganglion (DRG) neurons. The immunoreactivity of ribosomal protein P0/1/2 and S6, and novel protein synthesis were observed in the central, sterically bulky region of growth cones...
May 7, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29734780/cpkc%C3%AE-modulated-sequential-reactivation-of-mtor-inhibited-autophagic-flux-in-neurons-exposed-to-oxygen-glucose-deprivation-reperfusion
#13
Rongrong Hua, Song Han, Nan Zhang, Qingqing Dai, Ting Liu, Junfa Li
We have reported that conventional protein kinase Cγ (cPKCγ)-modulated neuron-specific autophagy improved the neurological outcome of mice following ischemic stroke through the Akt-mechanistic target of rapamycin (mTOR) pathway. However, its detailed molecular mechanism remains unclear. In this study, primary cortical neurons from postnatal one-day-old C57BL/6J cPKCγ wild-type ( cPKCγ +/+ ) and knockout ( cPKCγ −/− ) mice suffering oxygen glucose deprivation/reperfusion (OGD/R) were used to simulate ischemia/reperfusion injury in vitro...
May 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29729248/stimulation-dependent-remodeling-of-the-corticospinal-tract-requires-reactivation-of-growth-promoting-developmental-signaling-pathways
#14
Neela Zareen, Shahid Dodson, Kristine Armada, Rahma Awad, Nadia Sultana, Erina Hara, Heather Alexander, John H Martin
The corticospinal tract (CST) can become damaged after spinal cord injury or stroke, resulting in weakness or paralysis. Repair of the damaged CST is limited because mature CST axons fail to regenerate, which is partly because the intrinsic axon growth capacity is downregulated in maturity. Whereas CST axons sprout after injury, this is insufficient to recover lost functions. Chronic motor cortex (MCX) electrical stimulation is a neuromodulatory strategy to promote CST axon sprouting, leading to functional recovery after CST lesion...
May 2, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29729230/role-of-hypothalamus-in-aging-and-its-underlying-cellular-mechanisms
#15
REVIEW
Keetae Kim, Han Kyoung Choe
Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. In addition, functional alterations in a set of agouti-related peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons, a set of growth hormone-releasing hormone (GHRH) and somatostatin (SST) neurons, a set of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) neurons, and a set of gonadotropin-releasing hormone (GnRH) and kisspeptin/neurokinin B/dynorphin (KNDy) neurons contribute to age-related physiological decline in energy metabolism, hormone regulation, circadian rhythm, and reproduction, respectively...
May 2, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29728793/metformin-protects-against-spinal-cord-injury-by-regulating-autophagy-via-the-mtor-signaling-pathway
#16
Yue Guo, Fang Wang, Haopeng Li, Hui Liang, Yuhuan Li, Zhengchao Gao, Xijing He
Spinal cord injury (SCI) is a serious central trauma, leading to severe dysfunction of motor and sensory systems. Secondary injuries, such as apoptosis and cell autophagy, significantly impact the motor function recovery process. Metformin is a widely used oral anti-diabetic agent for type 2 diabetes in the world. It has been demonstrated to promote autophagy and inhibit apoptosis in the nervous system. However, its role in recovery following SCI is still unknown. In this study, we determined that motor function, assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor assessment scale, was significantly higher in rats treated with metformin following injury...
May 4, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29727771/bifenthrin-causes-transcriptomic-alterations-in-mtor-and-ryanodine-receptor-dependent-signaling-and-delayed-hyperactivity-in-developing-zebrafish-danio-rerio
#17
Daniel F Frank, Galen W Miller, Danielle J Harvey, Susanne M Brander, Juergen Geist, Richard E Connon, Pamela J Lein
Over the last few decades, the pyrethroid insecticide bifenthrin has been increasingly employed for pest control in urban and agricultural areas, putting humans and wildlife at increased risk of exposure. Exposures to nanomolar (nM) concentrations of bifenthrin have recently been reported to alter calcium oscillations in rodent neurons. Neuronal calcium oscillations are influenced by ryanodine receptor (RyR) activity, which modulates calcium-dependent signaling cascades, including the mechanistic target of rapamycin (mTOR) signaling pathway...
April 18, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29725084/loss-of-tctn3-causes-neuronal-apoptosis-and-neural-tube-defects-in-mice
#18
Bin Wang, Yingying Zhang, Hongli Dong, Siyi Gong, Bin Wei, Man Luo, Hongyan Wang, Xiaohui Wu, Wei Liu, Xingshun Xu, Yufang Zheng, Miao Sun
Tctn3 belongs to the Tectonic (Tctn) family and is a single-pass membrane protein localized at the transition zone of primary cilia as an important component of ciliopathy-related protein complexes. Previous studies showed that mutations in Tctn1 and Tctn2, two members of the tectonic family, have been reported to disrupt neural tube development in humans and mice, but the functions of Tctn3 in brain development remain elusive. In this study, Tctn3 knockout (KO) mice were generated by utilizing the piggyBac (PB) transposon system...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29712777/palladin-is-a-neuron-specific-translational-target-of-mtor-signaling-that-regulates-axon-morphogenesis
#19
Yusuke Umegaki, Antonio Martinéz Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi
The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein Palladin, which is localized within the cell body and axons in hippocampal neurons...
April 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29702408/dysregulated-long-non-coding-rnas-in-the-temporal-lobe-epilepsy-mouse-model
#20
Yoonhyuk Jang, Jangsup Moon, Soon-Tae Lee, Jin-Sun Jun, Tae-Joon Kim, Jung-Ah Lim, Byeong-Su Park, Jung-Suk Yu, Dong-Kyu Park, Ah Reaum Yang, Kyung-Ii Park, Ki-Young Jung, Manho Kim, Keun-Hwa Jung, Daejong Jeon, Kon Chu, Sang Kun Lee
PURPOSE: To perform comprehensive profiling of long non-coding RNAs (LncRNAs) in temporal lobe epilepsy. METHODS: We performed extensive profiling of LncRNAs and mRNAs in the mouse pilocarpine model in specific brain regions, the hippocampus and cortex, and compared the results to those of the control mouse. Differentially expressed LncRNAs and mRNAs were identified with a microarray analysis (Arraystar Mouse LncRNA Expression Microarray V3.0). Then, gene ontology (GO) and pathway analysis were performed to investigate the potential roles of the differentially expressed mRNAs in the pilocarpine model...
April 13, 2018: Seizure: the Journal of the British Epilepsy Association
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