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https://www.readbyqxmd.com/read/28888073/selective-decline-of-neurotrophin-and-neurotrophin-receptor-genes-within-ca1-pyramidal-neurons-and-hippocampus-proper-correlation-with-cognitive-performance-and-neuropathology-in-mild-cognitive-impairment-and-alzheimer-s-disease
#1
Stephen D Ginsberg, Michael H Malek-Ahmadi, Melissa J Alldred, Shaoli Che, Irina Elarova, Yinghua Chen, Freddy Jeanneteau, Thorsten M Kranz, Moses V Chao, Scott E Counts, Elliott J Mufson
Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections...
September 9, 2017: Hippocampus
https://www.readbyqxmd.com/read/28884193/neurotrophin-trk-receptors-new-targets-for-cancer-therapy
#2
Jacopo Meldolesi
In the last few years, exciting reports have emerged regarding the role of the two types of neurotrophin receptors, p75(NTR) and Trks, not only in neurons, where they were discovered, but also in non-neural cells and, especially, in numerous cancers, including breast, lung, colon-rectum, pancreas, prostate, glioblastoma, neuroblastoma, myeloma, and lymphoid tumors. Traditionally, p75(NTR), activated by all neurotrophins and their precursors, is an inhibitor. In various cancers, however, activated p75(NTR) induces variable effects, from inhibition to stimulation of cell proliferation, dependent on their direct or coordinate/indirect mechanism(s) of action...
September 8, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28865235/effect-of-electro-acupuncture-on-neuroplasticity-of-spinal-cord-transected-rats
#3
Xuyang Wang, Shiming Ju, Shiwen Chen, Wenwei Gao, Jun Ding, Gan Wang, Heli Cao, Hengli Tian, Xiaoli Li
BACKGROUND This study aimed to evaluate the effects of electro-acupuncture (EA) on neuroplasticity associated with the expressions of neurotrophic factors (NTFs) and their receptors in rats subjected to spinal cord transection (SCT). MATERIAL AND METHODS A total of 144 rats were randomly divided into 3 groups (n=48 per group): sham-operated group, SCT group, and EA (electro-acupuncture) group. Rats in SCT and EA groups received spinal cord transection at T10-T11 vertebral levels. Then, EA group rats received EA treatment...
September 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28829946/the-proprioceptive-system-masterminds-spinal-alignment-insight-into-the-mechanism-of-scoliosis
#4
Ronen Blecher, Sharon Krief, Tal Galili, Inbal E Biton, Tomer Stern, Eran Assaraf, Ditsa Levanon, Elena Appel, Yoram Anekstein, Gabriel Agar, Yoram Groner, Elazar Zelzer
Maintaining posture requires tight regulation of the position and orientation of numerous spinal components. Yet, surprisingly little is known about this regulatory mechanism, whose failure may result in spinal deformity as in adolescent idiopathic scoliosis. Here, we use genetic mouse models to demonstrate the involvement of proprioception in regulating spine alignment. Null mutants for Runx3 transcription factor, which lack TrkC neurons connecting between proprioceptive mechanoreceptors and spinal cord, developed peripubertal scoliosis not preceded by vertebral dysplasia or muscle asymmetry...
August 21, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28739680/bdnf-an-oncogene-or-tumor-suppressor
#5
REVIEW
Daniel P Radin, Parth Patel
Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF)...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28708822/an-ancient-neurotrophin-receptor-code-a-single-runx-cbf%C3%AE-complex-determines-somatosensory-neuron-fate-specification-in-zebrafish
#6
Philia Gau, Andrew Curtright, Logan Condon, David W Raible, Ajay Dhaka
In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28695340/tropomyosin-receptor-kinase-c-trkc-expression-in-medulloblastoma-relation-to-the-molecular-subgroups-and-impact-on-treatment-response
#7
Carsten Friedrich, Tarek Shalaby, Christoph Oehler, Martin Pruschy, Burkhardt Seifert, Daniel Picard, Marc Remke, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Stefan Rutkowski, Michael A Grotzer, André O von Bueren
PURPOSE: High messenger RNA (mRNA) expression of the tropomyosin receptor kinase C gene (TrkC) has been associated with favorable survival in medulloblastoma patients. Untested is whether it plays a role through modulating the response to therapy or whether it might be a surrogate marker for a favorable molecular subgroup. METHODS: The medulloblastoma-derived cell line DAOY was stably transfected to overexpress TrkC (clone DAOY-TrkC) and compared to a control (clone DAOY-EV, empty vector transfected)...
July 10, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28625641/emergence-of-novel-and-dominant-acquired-egfr-solvent-front-mutations-at-gly796-g796s-r-together-with-c797s-r-and-l792f-h-mutations-in-one-egfr-l858r-t790m-nsclc-patient-who-progressed-on-osimertinib
#8
Sai-Hong Ignatius Ou, Jean Cui, Alexa B Schrock, Michael E Goldberg, Viola W Zhu, Lee Albacker, Philip J Stephens, Vincent A Miller, Siraj M Ali
Acquired epidermal growth factor receptor (EGFR) resistance mutations to osimertinib are common, including the EGFR C797S that abolishes the covalent binding of osimertinib to EGFR. Here we report the emergence of novel EGFR solvent front mutations at Gly796 (G796S/R) in addition to a hinge pocket L792F/H mutations, and C797S/G all in cis with T790M in a single patient on progression on osimertinib as detected by plasma circulating tumor DNA (ctDNA) assay in the course of clinical care. A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28614398/5-aza-2-deoxycytidine-in-the-medial-prefrontal-cortex-regulates-alcohol-related-behavior-and-ntf3-trkc-expression-in-rats
#9
Xiaomeng Qiao, Fangyuan Yin, Yuanyuan Ji, Yunxiao Li, Peng Yan, Jianghua Lai
Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC). Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test...
2017: PloS One
https://www.readbyqxmd.com/read/28604655/brain-derived-neurotrophic-factor-tropomyosin-related-kinase-b-signaling-pathway-contributes-to-the-aggressive-behavior-of-lung-squamous-cell-carcinoma
#10
Keigo Ozono, Yoshihiro Ohishi, Hideya Onishi, Katsuya Nakamura, Junichi Motoshita, Masato Kato, Ryoichi Nakanishi, Masafumi Nakamura, Yoshinao Oda
The tropomyosin-related kinase (Trk) family consists of TrkA, TrkB, and TrkC, which play essential roles in tumor progression and/or suppression in various cancers. Little is known about the biological significance of the Trk family in human lung squamous cell carcinoma (SCC). Here we investigated the clinical significance of the protein expression of Trk family members in samples from 99 SCC patients, and we explored the relationship between invasion/proliferation activities and Trk expression using lung SCC cell lines to clarify the biological significance of the Trk family in lung SCC...
June 12, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28589908/activation-of-trka-receptor-elicits-mastocytosis-in-mice-and-is-involved-in-the-development-of-resistance-to-kit-targeted-therapy
#11
Min Yang, Zengkai Pan, Kezhi Huang, Guntram Büsche, Friedrich Feuerhake, Anuhar Chaturvedi, Danian Nie, Michael Heuser, Felicitas Thol, Nils von Neuhoff, Arnold Ganser, Zhixiong Li
The neurotrophins (NTs) play a key role in neuronal survival and maintenance. The TRK (tropomyosin-related kinase) tyrosine kinase receptors (TRKA, TRKB, TRKC) are high affinity receptors for NTs. There is increasing data demonstrating an important role of the TRK family in cancer initiation and progression. NTs have been known for many years to promote chemotaxis, maturation, and survival of mast cells. However, the role of NT signaling in the pathogenesis of mastocytosis is not well understood. In this study, we demonstrate that activation of TRKA by its ligand nerve growth factor (NGF) is potent to trigger a disease in mice with striking similarities to human systemic mastocytosis (SM)...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515680/trk-receptors-and-neurotrophin-cross-interactions-new-perspectives-toward-manipulating-therapeutic-side-effects
#12
Yazan Haddad, Vojtěch Adam, Zbyněk Heger
Some therapeutic side-effects result from simultaneous activation of homolog receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC) play a major role in the development and biology of neurons through neurotrophin signaling. The wide range of cross-interactions between Trk receptors and neurotrophins vary in selectivity, affinity and function. In this study, we discuss new perspectives to the manipulation of side-effects via a better understanding of the cross-interactions at the molecular level, derived by computational methods...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28455963/trkc-promotes-colorectal-cancer-growth-and-metastasis
#13
Min Soo Kim, Kwang Wook Suh, Suntaek Hong, Wook Jin
The current work reveals that TrkC receptor is crucial to many aspects of tumorigenicity and metastasis of cancer. However, with only a few exceptions, such as colorectal cancer (CRC), where suppressing tumorigenic and metastatic ability via expression of TrkC as tumor suppressor have been proposed. These diverse lines of evidence led us to investigate whether TrkC is involved in CRC progression. By using mouse models and molecular biology analyses, we demonstrate that TrkC acts as an activator in tumorigenicity and metastasis of colorectal cancer...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440877/brain-derived-neurotrophic-factor-neurotrophin-3-regulate-axon-initial-segment-location-and-affect-neuronal-excitability-in-cultured-hippocampal-neurons
#14
Yu Guo, Zi-Jun Su, Yi-Kun Chen, Zhen Chai
Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28404842/an-immortalized-human-dorsal-root-ganglion-cell-line-provides-a-novel-context-to-study-herpes-simplex-virus-1-latency-and-reactivation
#15
Nikki M Thellman, Carolyn Botting, Zachary Madaj, Steven J Triezenberg
A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-myc oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin...
June 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28402394/autophagy-and-trkc-nt-3-signaling-joined-forces-boost-the-hypoxic-glioblastoma-cell-survival
#16
Soha Jawhari, Barbara Bessette, Sophie Hombourger, Karine Durand, Aurélie Lacroix, François Labrousse, Marie-Odile Jauberteau, Marie-Hélène Ratinaud, Mireille Verdier
Glioblastoma multiform (GBM), the most common and aggressive primary brain tumor, is characterized by a high degree of hypoxia and resistance to therapy because of its adaptation capacities, including autophagy and growth factors signaling. In this study, we show an efficient hypoxia-induced survival autophagy in four different GBM cell lines (U87MG, M059K, M059J and LN-18) and an activation of a particular neurotrophin signaling pathway. Indeed, the enhancement of both TrkC and NT-3 was followed by downstream p38MAPK phosphorylation, suggesting the occurrence of a survival autocrine loop...
June 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28398601/antidepressant-imipramine-protects-bupivacaine-induced-neurotoxicity-in-dorsal-root-ganglion-neurons-through-co-activation-of-trka-and-trkb
#17
Jianrong Guo, Huan Wang, Qiang Tao, Shiyu Sun, Li Liu, Jianping Zhang, Dawei Yang
PURPOSE: In our work, we used an in vitro culture model to investigate whether antidepressant imipramine (Ip) may protect bupivacaine (Bv)-induced neurotoxicity in mouse dorsal root ganglion (DRG). METHODS: Adult mouse DRG was treated with 5 mM Bv in vitro to induce neurotoxicity. DRG was then pre-treated with Ip, prior to Bv, to examine its effects on protecting Bv-induced DRG apoptosis and neurite degeneration. Ip-induced dynamic changes in Trk receptors, including TrkA/B/C and phosphor (p-)TrkA/B/C, were examined by qPCR and western blot...
April 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28370021/roles-of-neurotrophins-in-skeletal-tissue-formation-and-healing
#18
REVIEW
Yu-Wen Su, Xin-Fu Zhou, Bruce K Foster, Brian L Grills, Jiake Xu, Cory J Xian
Neurotrophins and their receptors are key molecules that are known to be critical in regulating nervous system development and maintenance and have been recognized to be also involved in regulating tissue formation and healing in skeletal tissues. Studies have shown that neurotrophins and their receptors are widely expressed in skeletal tissues, implicated in chondrogenesis, osteoblastogenesis, and osteoclastogenesis, and are also involved in regulating tissue formation and healing events in skeletal tissue...
March 30, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28360836/genetic-tracing-of-cav3-2-t-type-calcium-channel-expression-in-the-peripheral-nervous-system
#19
Yinth A Bernal Sierra, Julia Haseleu, Alexey Kozlenkov, Valérie Bégay, Gary R Lewin
Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28347639/neurite-outgrowth-in-cultured-mouse-pelvic-ganglia-effects-of-neurotrophins-and-bladder-tissue
#20
Mari Ekman, Baoyi Zhu, Karl Swärd, Bengt Uvelius
Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro...
March 18, 2017: Autonomic Neuroscience: Basic & Clinical
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