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bdnf AND p75

Emmanuel Darcq, Nadege Morisot, Khanhky Phamluong, Vincent Warnault, Jerome Jeanblanc, Frank M Longo, Stephen M Massa, Dorit Ron
UNLABELLED: Brain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) keeps alcohol intake in moderation. For example, activation of the BDNF receptor tropomyosin receptor kinase B (TrkB) in the DLS reduces intake in rats that consume moderate amounts of alcohol. Here, we tested whether long-term excessive consumption of alcohol produces neuroadaptations in BDNF signaling in the rat DLS. We found that BDNF was no longer able to gate alcohol self-administration after a history of repeated cycles of binge alcohol drinking and withdrawal...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ting-Ting Wang, Chan Tian, Jing Sun, Hui Wang, Bao-Yun Zhang, Cao Chen, Jing Wang, Kang Xiao, Li-Na Chen, Yan Lv, Chen Gao, Qi Shi, Yan Xin, Xiao-Ping Dong
Prion is a unique nucleic acid-free pathogen that causes human and animal fatal neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. There are two distinct classes of glycosylated receptors, neurotrophin receptor p75 (p75NTR) and tropomyosin-related kinase (Trk), that can bind to BDNF. To obtain insights into the possible alterations of brain BDNF and its signaling pathway in prion disease, the levels of BDNF and several molecules in the BDNF pathway in the brain tissues of scrapie agents 263K-infected hamsters were separately evaluated...
October 2016: International Journal of Biochemistry & Cell Biology
Agung Dewanto, Jozsef Dudas, Rudolf Glueckert, Sylvia Mechsner, Anneliese Schrott-Fischer, Ludwig Wildt, Beata Seeber
BACKGROUND: The roles of the neurotrophins NGF (Neurotrophic growth factor) and BDNF (brain-derived neurotrophic factor) in neuronal growth and development are already known. Meanwhile, the neurotrophin receptors TrkA (tropomyosin related kinase A), TrkB, and p75 are important for determining the fate of cells. In endometriosis, this complex system has not been fully elucidated yet. The aim of this study was to evaluate the expression and location of these neurotrophins and their receptors in peritoneal (PE) and deep infiltrating endometriotic (DIE) tissues and to measure and compare the density of nerve fibers in the disease subtypes...
2016: Reproductive Biology and Endocrinology: RB&E
S Glerup, U Bolcho, S Mølgaard, S Bøggild, C B Vaegter, A H Smith, J L Nieto-Gonzalez, P L Ovesen, L F Pedersen, A N Fjorback, M Kjolby, H Login, M M Holm, O M Andersen, J R Nyengaard, T E Willnow, K Jensen, A Nykjaer
SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we report that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75(NTR), required for pro-brain-derived neurotrophic factor (BDNF) to induce long-term depression, and with the BDNF receptor tyrosine kinase TrkB to elicit long-term potentiation...
July 26, 2016: Molecular Psychiatry
Eero Castrén, Masami Kojima
Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment. These data, together with a wealth of reports using different animal models with depression-like behavior or manipulation of expression of BDNF or its receptor TrkB have implicated BDNF in the pathophysiology of depression as well as in the mechanism of action of antidepressant treatments. Recent findings have shown that posttranslational processing of BDNF gene product can yield different molecular entities that differently influence signaling through BNDF receptor TrkB and the pan-neurotrophin receptor p75(NTR)...
July 15, 2016: Neurobiology of Disease
Tao Yang, Stephen M Massa, Kevin C Tran, Danielle A Simmons, Jayakumar Rajadas, Anne Y Zeng, Taichang Jang, Sara Carsanaro, Frank M Longo
Neurotrophin (NT) receptors are coupled to numerous signaling networks that play critical roles in neuronal survival and plasticity. Several non-peptide small molecule ligands have recently been reported that bind to and activate specific tropomyosin-receptor kinase (Trk) NT receptors, stimulate their downstream signaling, and cause biologic effects similar to, though not completely overlapping, those of the native NT ligands. Here, in silico screening, coupled with low-throughput neuronal survival screening, identified a compound, LM22B-10, that, unlike prior small molecule Trk ligands, binds to and activates TrkB as well as TrkC...
November 2016: Neuropharmacology
Yin-Yin Bai, Chun-Sheng Ruan, Chun-Rui Yang, Jia-Yi Li, Zhi-Long Kang, Li Zhou, Dennis Liu, Yue-Qing Zeng, Tin-Hua Wang, Chang-Fu Tian, Hong Liao, Larisa Bobrovskaya, Xin-Fu Zhou
Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. BDNF has long been investigated for its positive role in regulation of mood, while the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced up-regulation of proBDNF was abolished by chronic administration of fluoxetine...
June 17, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Beatrice M Girard, Susan Malley, Victor May, Margaret A Vizzard
We have determined if cyclophosphamide (CYP)-induced cystitis produces additional changes in growth factor/receptors expression in the urinary bladder (urothelium, detrusor) and lumbosacral (L6-S1) dorsal root ganglia (DRG) in a transgenic mouse model with chronic urothelial overexpression of NGF (NGF-OE). Functionally, NGF-OE mice treated with CYP exhibit significant increases in voiding frequency above that observed in control NGF-OE mice (no CYP). Quantitative PCR was used to determine NGF, BDNF, VEGF, and receptors (TrkA, TrkB, p75(NTR)) transcripts expression in tissues from NGF-OE and wild-type (WT) mice with CYP-induced cystitis of varying duration (4 h, 48 h, 8 days)...
August 2016: Journal of Molecular Neuroscience: MN
Cong Luo, Xiao-Lin Zhong, Fiona H Zhou, Jia-Yi Li, Pei Zhou, Jun-Mei Xu, Bo Song, Chang-Qi Li, Xin-Fu Zhou, Ru-Ping Dai
The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain...
2016: Scientific Reports
A Gonzalez, G Moya-Alvarado, C Gonzalez-Billaut, F C Bronfman
Brain-derived neurotrophic factor (BDNF) and its receptors TrkB and p75 regulate dendritic and axonal growth during development and maintenance of the mature nervous system; however, the cellular and molecular mechanisms underlying this process are not fully understood. In recent years, several advances have shed new light on the processes behind the regulation of BDNF-mediated structural plasticity including control of neuronal transcription, local translation of proteins, and regulation of cytoskeleton and membrane dynamics...
May 25, 2016: Cytoskeleton
Miguel A De la Cruz-Morcillo, Julien Berger, Ricardo Sánchez-Prieto, Sofiane Saada, Thomas Naves, Angélique Guillaudeau, Aurélie Perraud, Philippe Sindou, Aurélie Lacroix, Aurélien Descazeaud, Fabrice Lalloué, Marie-Odile Jauberteau
p75NTR, a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/or p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated...
June 7, 2016: Oncotarget
Chun-Sheng Ruan, Chun-Rui Yang, Jia-Yi Li, Hai-Yun Luo, Larisa Bobrovskaya, Xin-Fu Zhou
Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established...
July 2016: Experimental Neurology
G Zunino, A Messina, P Sgadò, G Baj, S Casarosa, Y Bozzi
Engrailed-2 (En2), a homeodomain transcription factor involved in regionalization and patterning of the midbrain and hindbrain regions has been associated to autism spectrum disorders (ASDs). En2 knockout (En2(-/-)) mice show ASD-like features accompanied by a significant loss of GABAergic subpopulations in the hippocampus and neocortex. Brain-derived neurotrophic factor (BDNF) is a crucial factor for the postnatal development of forebrain GABAergic neurons, and altered GABA signaling has been hypothesized to underlie the symptoms of ASD...
June 2, 2016: Neuroscience
A B Wehner, A M Milen, R L Albin, B A Pierchala
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a constellation of motor, cognitive, and psychiatric features. Striatal medium spiny neurons, one of the most affected populations, are dependent on brain-derived neurotrophic factor (BDNF) anterogradely transported from the cortex for proper function and survival. Recent studies suggest both receptors for BDNF, TrkB and p75 neurotrophin receptor (p75), are improperly regulated in the striata of HD patients and mouse models of HD...
June 2, 2016: Neuroscience
Mariana Colino-Oliveira, Diogo M Rombo, Raquel B Dias, Joaquim A Ribeiro, Ana M Sebastião
Brain-derived neurotrophic factor (BDNF) and adenosine are widely recognized as neuromodulators of glutamatergic transmission in the adult brain. Most BDNF actions upon excitatory plasticity phenomena are under control of adenosine A2A receptors (A2ARs). Concerning gamma-aminobutyric acid (GABA)-mediated transmission, the available information refers to the control of GABA transporters. We now focused on the influence of BDNF and the interplay with adenosine on phasic GABAergic transmission. To assess this, we evaluated evoked and spontaneous synaptic currents recorded from CA1 pyramidal cells in acute hippocampal slices from adult rat brains (6 to 10 weeks old)...
June 2016: Purinergic Signalling
Riyaz Mohamed, Azza B El-Remessy
Diabetic retinopathy is the leading cause of blindness in working age in US and worldwide. Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) are known to be essential for growth, differentiation and survival of neurons in the developing and mature retina. Nevertheless, a growing body of evidence supports an emerging role of neurotrophins in retinal diseases and in particular, diabetic retinopathy. Neurotrophins are initially synthesized in a pro-form and undergo proteolytic cleavage to produce the mature form that activates two distinctive receptors, the tyrosine kinase tropomycin receptor (Trk) and, to lesser extent, the common low affinity p75 neurotrophin receptor (p75(NTR))...
October 2015: Journal of Clinical & Experimental Ophthalmology
L Y Qiao, S Shen, M Liu, C Xia, J C Kay, Q L Zhang
Brain-derived neurotrophic factor (BDNF) release to nerve terminals in the central nervous system is crucial in synaptic transmission and neuronal plasticity. However, BDNF release peripherally from primary afferent neurons has not been investigated. In the present study, we show that BDNF is synthesized by primary afferent neurons located in the dorsal root ganglia (DRG) in rat, and releases to spinal nerve terminals in response to depolarization or visceral inflammation. In two-compartmented culture that separates DRG neuronal cell bodies and spinal nerve terminals, application of 50mM K(+) to either the nerve terminal or the cell body evokes BDNF release to the terminal compartment...
March 24, 2016: Neuroscience
Antonella Marte, Mirko Messa, Fabio Benfenati, Franco Onofri
Synapsins (Syns) are synaptic vesicle-associated phosphoproteins involved in neuronal development and neurotransmitter release. While Syns are implicated in the regulation of brain-derived neurotrophic factor (BDNF)-induced neurotransmitter release, their role in the BDNF developmental effects has not been fully elucidated. By using primary cortical neurons from Syn I knockout (KO) and Syn I/II/III KO mice, we studied the effects of BDNF and nerve growth factor (NGF) on axonal growth. While NGF had similar effects in all genotypes, BDNF induced significant differences in Syn KO axonal outgrowth compared to wild type (WT), an effect that was rescued by the re-expression of Syn I...
January 7, 2016: Molecular Neurobiology
Ruhui Lin, Jixiang Chen, Xiaojie Li, Jingjie Mao, Yunan Wu, Peiyuan Zhuo, Yinzheng Zhang, Weilin Liu, Jia Huang, Jing Tao, Li-Dian Chen
Alzheimer's disease (AD) is a common human neurodegenerative disorder characterized by progressive deterioration of cognition and memory. Acupuncture at the Baihui (DU20) acupoint has long been used in China to clinically treat cognitive impairment. However, the precise mechanism underlying its neuroprotective effects remains to be elucidated. In the present study, electroacupuncture (EA) at the Baihui (DU20) acupoint was observed to markedly ameliorate cognitive impairments, reduce the aberrant overexpression of β-amyloid(1-42), and inhibit neuronal apoptosis in APP/PS1 mice...
February 2016: Molecular Medicine Reports
Silvina Laura Diaz, Nicolas Narboux-Nême, Katia Boutourlinsky, Stéphane Doly, Luc Maroteaux
Depressive disorders are among the most prevalent neuropsychiatric dysfunctions worldwide, with high rates of resistance to antidepressant treatment. Genetic factors clearly contribute to the manifestation of depression as well as to the response to antidepressants. Transgenic mouse models appear as seminal tools to disentangle this complex disorder. Here, we analyzed new key aspects of the phenotype of knock-out mice for the gene encoding the serotonin 2B receptor (Htr(2B)(-/-)), including basal phenotype, ability to develop a depressive-like phenotype upon chronic isolation, and effect of chronic exposure to fluoxetine on chronically stressed Htr(2B)(-/-) mice...
February 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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