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https://www.readbyqxmd.com/read/29242531/long-noncoding-rna-expression-profile-reveals-lncrnas-signature-associated-with-extracellular-matrix-degradation-in-kashin-beck-disease
#1
Cuiyan Wu, Huan Liu, Feng'e Zhang, Wanzhen Shao, Lei Yang, Yujie Ning, Sen Wang, Guanghui Zhao, Byeong Jae Lee, Mikko Lammi, Xiong Guo
Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29239329/activation-of-the-akt-mtor-signaling-pathway-a-potential-response-to-long-term-neuronal-loss-in-the-hippocampus-after-sepsis
#2
Jia-Nan Guo, Lin-Yu Tian, Wen-Yu Liu, Jie Mu, Dong Zhou
Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR) and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a "self-rescuing" feedback response to neuronal loss after sepsis...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29233655/recombinant-human-erythropoietin-protects-against-brain-injury-through-blunting-the-mtorc1-pathway-in-the-developing-brains-of-rats-with-seizures
#3
Qinrui Li, Ying Han, Junbao Du, Hongfang Jin, Jing Zhang, Manman Niu, Jiong Qin
AIMS: Recurrent seizures can result in neuronal death, cognitive deficits and intellectual disability, which causes devastating damage in children. Recombinant human erythropoietin (rhEPO) is considered a neuroprotective factor in many nervous system diseases. However, the precise mechanisms through which rhEPO exerts its neuroprotective effects on epilepsy remain unknown. Thus, in this study, we determined whether rhEPO protects against brain injury by inducing cortical neuronal autophagy through blunting the mammalian target of rapamycin complex 1 (mTORC1) pathway in the developing brains of rats with seizures...
December 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/29232822/microglia-m2a-polarization-as-potential-link-between-food-allergy-and-autism-spectrum-disorders
#4
REVIEW
Hans O Kalkman, Dominik Feuerbach
Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD). Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13), which stimulate microglia and macrophages to adopt a phenotype referred to as 'alternative activation' or 'M2A'. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1...
December 9, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29222553/ghrelin-attenuates-retinal-neuronal-autophagy-and-apoptosis-in-an-experimental-rat-glaucoma-model
#5
Ke Zhu, Meng-Lu Zhang, Shu-Ting Liu, Xue-Yan Li, Shu-Min Zhong, Fang Li, Ge-Zhi Xu, Zhongfeng Wang, Yanying Miao
Purpose: Ghrelin, a natural ligand for the growth hormone secretagogue receptor type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated neuroprotection with a rat chronic intraocular hypertension (COH) model. Methods: The rat COH model was produced by blocking episcleral veins. A combination of immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of retinal ganglion cells (RGCs) was used...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29218081/tetramethylpyrazine-phosphate-and-borneol-combination-therapy-synergistically-attenuated-ischemia-reperfusion-injury-of-the-hypothalamus-and-striatum-via-regulation-of-apoptosis-and-autophagy-in-a-rat-model
#6
Bin Yu, Ming Ruan, Tao Liang, Shi-Wen Huang, Sheng-Jin Liu, Hai-Bo Cheng, Xiang-Chun Shen
The combination of tetramethylpyrazine (TMP) and borneol (BO) has shown promise for treatment of cerebral ischemia in clinical and experimental studies. However, the mechanism for the synergistic effect of these compounds is unclear. In this study, global cerebral ischemia-reperfusion (GCIR) was induced in rats that were subsequently treated with tetramethylpyrazine phosphate (TMPP) (13.3 mg/kg), BO (0.16 g/kg), or the combination TMPP + BO. Neuronal ultrastructure and intracellular calcium [Ca2+]i levels were evaluated in hypothalamus and striatum...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29209172/the-role-of-netrin-1-in-improving-functional-recovery-through-autophagy-stimulation-following-spinal-cord-injury-in-rats
#7
Liangjie Bai, Xifan Mei, Yanfeng Wang, Yajiang Yuan, Yunlong Bi, Gang Li, Hongyu Wang, Peng Yan, Gang Lv
Our previous findings indicated that treatment with Netrin-1 could improve functional recovery through the stimulation of autophagy, by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway in rats following spinal cord injury (SCI). However, the underlying mechanisms were not elucidated. The purpose of this study was to investigate the underlying mechanisms by which Netrin-1 promotes autophagy and improves functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats, we observed that the autophagic flux in neurons was impaired, as reflected by the accumulation of light chain 3-II (LC3-II)-positive and LC3-positive autophagosomes (APs), accompanied by the accumulation of the autophagic substrate, Sequestosome 1 (SQSTM1; also known as p62)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29205090/rapamycin-exacerbates-cardiovascular-dysfunction-after-complete-high-thoracic-spinal-cord-injury
#8
Khalid C Eldahan, David H Cox, Jenna L Gollihue, Samir P Patel, Alexander G Rabchevsky
Autonomic dysreflexia (AD) is a potentially life-threatening syndrome in individuals with spinal cord injury (SCI) above the T6 spinal level that is characterized by episodic hypertension in response to noxious stimuli below the lesion. Maladaptive intraspinal plasticity is thought to contribute to the temporal development of AD, and experimental approaches that reduce such plasticity mitigate the severity of AD. The mammalian target of rapamycin (mTOR) has gained interest as a mediator of plasticity, regeneration and nociceptor hypersensitivity in the injured spinal cord...
December 5, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29201571/transcriptomic-profiling-of-mtor-and-ryanodine-receptor-signaling-molecules-in-developing-zebrafish-in-the-absence-and-presence-of-pcb-95
#9
Daniel F Frank, Galen W Miller, Richard E Connon, Juergen Geist, Pamela J Lein
The mechanistic target of rapamycin (mTOR) and ryanodine receptor (RyR) signaling pathways regulate fundamental processes of neurodevelopment, and genetic mutations within these pathways have been linked to neurodevelopmental disorders. While previous studies have established that these signaling molecules are expressed in developing zebrafish, a detailed characterization of the ontogenetic profile of these signaling molecules is lacking. Thus, we evaluated the spatiotemporal expression of key transcripts in mTOR and RyR signaling pathways in wildtype zebrafish at 24, 72 and 120 hours post fertilization (hpf)...
2017: PeerJ
https://www.readbyqxmd.com/read/29201556/ns-pten-knockout-mice-show-sex-and-age-specific-differences-in-ultrasonic-vocalizations
#10
Matthew S Binder, Joaquin N Lugo
Objective: The goal of this study was to identify changes in quantitative and qualitative aspects of neonatal ultrasonic vocalizations USVs in neuron-subset specific (NS-Pten) knockout males and females when compared with wild-type male and female mice. Background: One signaling cascade that plays a crucial role in the development of an autistic-like phenotype is the PI3K/Akt/mTOR pathway. Mouse models that illustrate this connection include Fmr1, Tsc1, and NS-Pten-deficient mice...
November 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29197516/protopanaxadiol-derivative-ddpu-improves-behavior-and-cognitive-deficit-in-ad-mice-involving-regulation-of-both-er-stress-and-autophagy
#11
Xiaodan Guo, Jianlu Lv, Jian Lu, Lei Fan, Xi Huang, Lihong Hu, Jiaying Wang, Xu Shen
Alzheimer's disease (AD) is a progressively neurodegenerative disease with typical hallmarks of amyloid β (Aβ) plaque accumulation, neurofibrillary tangle (NFT) formation and neuronal death extension. Aggressive Aβ accumulation promotes senile plaque formation and perturbs endoplasmic reticulum (ER) function to trigger the unfolded protein response (UPR) leading to neuronal apoptosis. The stress-dependent activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) increases the phosphorylation of eukaryotic translation initiation factor-2α (eIF2α) to promote the preferential synthesis of β-site APP cleavage enzyme 1 (BACE1) and Aβ generation in turn...
November 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29186197/fingolimod-suppresses-neuronal-autophagy-through-the-mtor-p70s6k-pathway-and-alleviates-ischemic-brain-damage-in-mice
#12
Xiao Li, Ming-Huan Wang, Chuan Qin, Wen-Hui Fan, Dai-Shi Tian, Jun-Li Liu
The bioactive, signaling lipid, sphingosine-1-phosphate (S1P), and its analog, fingolimod (FTY720), have previously shown neuroprotective effects against ischemic brain injury. However, the underlying mechanisms have not yet been fully clarified. The roles of autophagy in ischemic stroke are being increasingly recognized. In the present study, we sought to determine whether the S1P pathway is involved in neuronal autophagy and investigate its possible mechanisms following stroke. Interestingly, we found that FTY720 significantly attenuates infarct volumes and reduces neuronal apoptosis on days 1 and 3 post stroke, accompanied by amelioration of functional deficits...
2017: PloS One
https://www.readbyqxmd.com/read/29183728/lycium-barbarum-polysaccharide-protects-against-oxygen-glucose-deprivation-reoxygenation-induced-apoptosis-and-autophagic-cell-death-via-the-pi3k-akt-mtor-signaling-pathway-in-primary-cultured-hippocampal-neurons
#13
Yang Yu, Xiuquan Wu, Jingnan Pu, Peng Luo, Wenke Ma, Jiu Wang, Jialiang Wei, Yuanxin Wang, Zhou Fei
Lycium barbarum polysaccharide (LBP) is the main active ingredient of Lycium barbarum, which exhibits several beneficial effects, including neuroprotection, anti-aging and anti-oxidation. However, the mechanism by which LBP protects against cerebral ischemia/reperfusion-induced injury remains obscure. In this study, we found that LBP pretreatment greatly attenuated oxygen glucose deprivation/reperfusion (OGD/R) injury in primary cultured hippocampal neurons. LBP also suppressed OGD/R-induced lactate dehydrogenase (LDH) leakage, and ameliorated oxidative stress...
November 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29178548/preservation-of-neuronal-functions-by-exosomes-derived-from-different-human-neural-cell-types-under-ischemic-conditions
#14
Mingyang Deng, Han Xiao, Hongling Peng, Huan Yuan, Yunxiao Xu, Guangsen Zhang, Jianguang Tang, Zhiping Hu
Stem cell based therapies have been reported in protecting cerebral infarction induced neuronal dysfunction and death. However, most studies used rat/mouse neuron as model cell when treated with stem cell or exosomes. Whether these findings can be translated from rodent to humans has been in doubt. Here, we used human embryonic stem cell derived neurons to detect the protective potential of exosomes against ischemia. Neurons were treated with in vitro oxygen-glucose deprivation (OGD) for 1 hour. For treatment group, different exosomes were derived from neuron, embryonic stem cell, neural progenitor cell and astrocyte differentiated from H9 human embryonic stem cell, and added to culture medium 30 min after OGD (100 μg/ml)...
November 27, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29174113/ghrelin-protects-retinal-ganglion-cells-against-rotenone-via-inhibiting-apoptosis-restoring-mitochondrial-function-and-activating-akt-mtor-signaling
#15
Shenwen Liu, Sheng Chen, Jing Ren, Baijun Li, Bo Qin
Ghrelin, a 28-amino acid peptide hormone, has protective effects on neuronal cells. The present study aimed to examine the neuroprotective effects of ghrelin on the rat retinal ganglion cells in the rotenone-induced in vitro model of Parkinson's disease (PD). Cell viability and cell apoptosis were determined by MTT assay and flow cytometry, respectively. Mitochondrial functions were detected by mitochondrial complex I activity assay and mitochondrial membrane potential (MMP) assay. The mRNA and protein expression levels were determined by qRT-PCR and western blot, respectively...
November 21, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29163060/nmda-receptors-regulate-the-development-of-neuronal-intrinsic-excitability-through-cell-autonomous-mechanisms
#16
Guoqiang Hou, Zhong-Wei Zhang
Maturation of neuronal and synaptic functions during early life is essential for the development of neuronal circuits and behaviors. In newborns synaptic transmission at excitatory synapses is primarily mediated by N-methyl-D-aspartate receptors (NMDARs), and NMDAR-mediated signaling plays an important role in synaptic maturation. Concomitant with synapse development, the intrinsic properties of neurons undergo dramatic changes during early life. However, little is known about the role of NMDARs in the development of intrinsic excitability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29161812/acute-amino-acid-d-serine-administration-similar-to-ketamine-produces-antidepressant-like-effects-through-the-identical-mechanisms
#17
I-Hua Wei, Kuang-Ti Chen, Mang-Hung Tsai, Ching-Hsiang Wu, Hsien-Yuan Lane, Chih-Chia Huang
D-serine is an amino acid and can work as an agonist at the glycine sites of N-methyl-D-aspartate receptor (NMDAR). Interestingly, both types of glutamatergic modulators, NMDAR enhancers and blockers, can improve depression through common targets, namely alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptors (AMPARs) and mammalian target of rapamycin (mTOR). To elucidate the cellular signaling pathway underlying this counterintuitive observation, we activated NMDARs in rats by using D-serine. Saline, ketamine (NMDAR antagonist), and desipramine (tricyclic antidepressant) were used as controls...
November 22, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#18
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#19
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29156769/liraglutide-activates-autophagy-via-glp-1r-to-improve-functional-recovery-after-spinal-cord-injury
#20
Jian Chen, Zhouguang Wang, Yuqin Mao, Zengming Zheng, Yu Chen, Sinan Khor, Kesi Shi, Zili He, Jiawei Li, Fanghua Gong, Yanlong Liu, Aiping Hu, Jian Xiao, Xiangyang Wang
Therapeutics used to treat central nervous system (CNS) injury are designed to promote axonal regeneration and inhibit cell death. Previous studies have shown that liraglutide exerts potent neuroprotective effects after brain injury. However, little is known if liraglutide treatment has neuroprotective effects after spinal cord injury (SCI). This study explores the neuroprotective effects of liraglutide and associated underlying mechanisms. Our results showed that liraglutide could improve recovery after injury by decreasing apoptosis as well as increasing microtubulin acetylation, and autophagy...
October 17, 2017: Oncotarget
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