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Li Zhou, Jing Xiong, Chun-Sheng Ruan, Ye Ruan, Dennis Liu, Jian-Jun Bao, Xin-Fu Zhou
Alcohol dependence is a worldwide problem with a great social and economic burden in many countries. A number of studies have suggested that BDNF (mature BDNF) and its precursor (proBDNF) play important roles in the alcohol dependence. However, what roles of the mBDNF/proBDNF pathways play during the pathological process of alcohol dependence are not clearly understood. In our clinical study, peripheral blood was sampled from 30 male patients with alcohol dependence and 50 healthy males (as control). The protein levels of proBDNF, p75NTR, sortilin, mBDNF, TrkB and mRNA levels of BDNF, p75NTR, sortilin, and TrkB were detected in the peripheral blood in our study...
March 9, 2018: Translational Psychiatry
Marta Maltese, Jennifer Stanic, Annalisa Tassone, Giuseppe Sciamanna, Giulia Ponterio, Valentina Vanni, Giuseppina Martella, Paola Imbriani, Paola Bonsi, Nicola Biagio Mercuri, Fabrizio Gardoni, Antonio Pisani
The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, though it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a +/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a +/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation...
March 5, 2018: ELife
Tatiana V Ilchibaeva, Anton S Tsybko, Rimma V Kozhemyakina, Elena M Kondaurova, Nina K Popova, Vladimir S Naumenko
Brain-derived neurotrophic factor (BDNF), its precursor proBDNF, BDNF pro-peptide, BDNF mRNA levels, as well as TrkB and p75NTR receptors mRNA and protein levels, were studied in the brain of rats, selectively bred for more than 85 generations for either the high level or the lack of fear-induced aggressive behavior. Furthermore, we have found that rats of aggressive strain demonstrated both high level of aggression toward humans and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression...
February 6, 2018: Behavioural Brain Research
Shih-Jen Tsai
Major depressive disorder is a common illness worldwide, but the pathogenesis of the disorder remains incompletely understood. The tissue-type plasminogen activator-plasminogen proteolytic cascade is highly expressed in the brain regions involved in mood regulation and neuroplasticity. Accumulating evidence from animal and human studies suggests that tissue-type plasminogen activator and its chief inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. Furthermore, the neurotrophic hypothesis of depression postulates that compromised neurotrophin brain-derived neurotrophic factor (BDNF) function is directly involved in the pathophysiology of depression...
December 22, 2017: Oncotarget
Bin Yi, Cong Wu, Runjie Shi, Kun Han, Haibin Sheng, Bei Li, Ling Mei, Xueling Wang, Zhiwu Huang, Hao Wu
HYPOTHESIS: We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). BACKGROUND: Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity...
March 2018: Otology & Neurotology
Mehreen Rahman, Haiyun Luo, Neil R Sims, Larisa Bobrovskaya, Xin-Fu Zhou
Treatment with mature brain-derived neurotrophic factor (mBDNF) promotes functional recovery after ischemia in animal trials but the possible role of its precursor protein proBDNF and its receptors or the factors responsible for the conversion of proBDNF to mBDNF in ischemic stroke are not known. The main aim of this study was to characterize the time-dependent expression of genes and/or proteins related to BDNF processing and signaling after ischemia as well as the sensorimotor behavioral dysfunction in a photothrombotic ischemic model in rats...
January 12, 2018: Neurochemical Research
Wei Sun, Xiaoliang Li, Lei An
Brain-derived neurotrophic factor (BDNF) has been investigated for its positive role in regulation of fear acquisition and memory. The precursor of BDNF, proBDNF, has been identified as different protein from its mature form. The prelimbic (PL) and infralimbic (IL) sub-regions of the medial prefrontal cortex (mPFC) are functionally distinct in fear behavior. However, the role of PL and IL proBDNF in fear memory is unclear. Here, through the infusion of cleavage-resistant proBDNF and its antibody, we identified the dissociable roles of PL and IL proBDNF in fear expression and extinction memory as well as explored proBDNF's potential mechanism of action...
December 11, 2017: Neuropharmacology
Dan-Dan Li, Hang Xie, Yi-Feng Du, Yan Long, Miranda N Reed, Mei Hu, Vishnu Suppiramaniam, Hao Hong, Su-Su Tang
BACKGROUND: Recent studies demonstrated beneficial effects of zileuton, a 5-lipoxygenase (5LO) inhibitor, on some brain diseases in animal models, but the role of zileuton in the depression remains unknown. METHODS: We investigated the effects of zileuton on depressive behaviors using tail suspension test (TST), forced swimming test (FST) and novelty-suppressed feeding test (NSFT) in mice injected with lipopolysaccharide (LPS). The 5LO level, activation of microglia, NF-κB p65, TNF-α, IL-1β, brain-derived neurotrophic factor (BDNF), and c-AMP response element-binding protein (CREB) were determined in the mouse hippocampus...
February 2018: Journal of Affective Disorders
Barbara A Mysona, Jing Zhao, Sylvia Smith, Kathryn E Bollinger
Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF's importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system...
February 2018: Experimental Eye Research
Mona Buhusi, Chris Etheredge, Ann-Charlotte Granholm, Catalin V Buhusi
Memory decline during aging or accompanying neurodegenerative diseases, represents a major health problem. Neurotrophins have long been considered relevant to the mechanisms of aging-associated cognitive decline and neurodegeneration. Mature Brain-Derived Neurotrophic Factor (BDNF) and its precursor (proBDNF) can both be secreted in response to neuronal activity and exert opposing effects on neuronal physiology and plasticity. In this study, biochemical analyses revealed that increased levels of proBDNF are present in the aged mouse hippocampus relative to young and that the level of hippocampal proBDNF inversely correlates with the ability to perform in a spatial memory task, the water radial arm maze (WRAM)...
2017: Frontiers in Aging Neuroscience
D V Bazovkina, E M Kondaurova, A S Tsybko, A I Kovetskaya, T V Ilchibaeva, V S Naumenko
Brain-derived neurotropic factor (BDNF) plays an important role in mechanisms of depression. Precursor protein of this factor (proBDNF) can initiate apoptosis in the brain, while the mature form of BDNF is involved in neurogenesis. It is known that chronic alcoholization leads to the activation of apoptotic processes, neurodegeneration, brain injury, and cognitive dysfunction. In this work, we have studied the influence of long-term ethanol exposure on the proBDNF and BDNF protein levels, as well as on the expression of genes that encode these proteins in the brain structures of ASC mice with genetic predisposition to depressive-like behavior and in mice from parental nondepressive CBA strain...
July 2017: Molekuliarnaia Biologiia
Shingo Enomoto, Kunio Shimizu, Masashi Nibuya, Eiji Suzuki, Kiyoshi Nagata, Takashi Kondo
Electroconvulsive therapy (ECT) is still the most effective strategy to treat severe and drug-resistant depressive disorders. Electroconvulsive seizure (ECS), which induces neuroplastic structural alterations and resilient behavioral changes in experimental animals, is the model of the ECT for human depression. ECT is typically administered three times per week for up to 4 weeks, while ECS treatments are administered daily for 10days. The increased expression of hippocampal brain-derived neurotrophic factor (BDNF) induced by antidepressive ECS treatment in experimental animals has been well documented...
November 1, 2017: Neuroscience Letters
Caitlin N Suire, Erez Eitan, Nancy Chiles Shaffer, Qu Tian, Stephanie Studenski, Mark P Mattson, Dimitrios Kapogiannis
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is produced by cleavage of proBDNF, and BDNF and proBDNF may play antagonistic roles in nervous system development, learning, memory and neuronal stress resistance. BDNF and proBDNF are present in blood, but the origin and relative contributions of soluble and extracellular vesicle (EV)-associated levels are unknown. METHODS: In this study we used validated immunoassays to measure proBDNF and BDNF levels in plasma, total plasma EVs and a subpopulation of EVs enriched for neuronal origin (expressing the neuronal marker L1CAM) in 150 Baltimore Longitudinal Study of Aging participants with and without decline in walking speed (reflecting aging-associated motor decline)...
November 2017: Experimental Gerontology
Cássia Sallaberry, Ana Paula Ardais, Andréia Rocha, Maurício Felisberto Borges, Gabriela T Fioreze, Sabrina Mioranzza, Fernanda Nunes, Natália Pagnussat, Paulo Henrique S Botton, Lisiane O Porciúncula
Few studies have addressed the effects of caffeine in the puberty and/or adolescence in a sex dependent manner. Considering that caffeine intake has increased in this population, we investigated the behavioral and synaptic proteins changes in pubescent male and female rats after maternal consumption of caffeine. Adult female Wistar rats started to receive water or caffeine (0.1 and 0.3g/L in drinking water; low and moderate dose, respectively) during the active cycle at weekdays, two weeks before mating. The treatment lasted up to weaning and the offspring received caffeine until the onset of puberty (30-34days old)...
August 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Alessia Bachis, Lee A Campbell, Kierra Jenkins, Erin Wenzel, Italo Mocchetti
Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of morphine withdrawal on BDNF and its precursor protein, or proBDNF, which induces neuronal apoptosis. In this work, we examined whether BDNF and proBDNF levels change in rats chronically injected with escalating doses of morphine and those who undergo spontaneous withdrawal for 60 h. We observed, in the frontal cortex and striatum, that the ratio of BDNF to proBDNF changed depending upon the experimental paradigm...
October 2017: Neurotoxicity Research
Suzhen Chen, Haitang Jiang, Yang Liu, Zhenhua Hou, Yingying Yue, Yuqun Zhang, Fuying Zhao, Zhi Xu, Yinghui Li, Xiaodong Mou, Lei Li, Tianyu Wang, Jingjing Zhao, Chongyang Han, Yuxiu Sui, Ming Wang, Zhong Yang, Yan Lu, Yifeng Zhu, Jianhua Li, Xinhua Shen, Fei Sun, Qingsong Chen, Huanxin Chen, Yonggui Yuan
Mental disorders are severe, disabling conditions with unknown etiology and are commonly misdiagnosed when clinical symptomology criteria are solely used. Our previous work indicated that combination of serum levels of multiple proteins in tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF) pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here, we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF, precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked immunosorbent assay kits...
July 31, 2017: Scientific Reports
Jia Chen, Tao Zhang, Shusheng Jiao, Xinfu Zhou, Jinhua Zhong, Yanjiang Wang, Juan Liu, Juan Deng, Shuiping Wang, Zhiqiang Xu
BACKGROUND: Alzheimer's disease (AD) is pathologically known for the amyloid-β (Aβ) deposition, neurofibrillary tangles, and neuronal loss in the brain. The precursor of brain-derived neurotrophic factor (proBDNF) before proteolysis has opposing functions to its mature form in neuronal survival and neurite growth. However, the role of proBDNF in the pathogenesis of AD remains unclear. OBJECTIVE: To investigate the effects of proBDNF on neurons in vitro, and on learning and memory impairment and brain Aβ production in a transgenic AD mouse model (APPswePS1dE9)...
2017: Journal of Alzheimer's Disease: JAD
Ana Paula Pesarico, Suzan G Rosa, Franciele Martini, Tales A Goulart, Gilson Zeni, Cristina Wayne Nogueira
Certain stressful life events have been associated with the onset of depression. This study aims to investigate if 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) is effective against social avoidance induced by social defeat stress model in mice. Furthermore, it was investigated the effects of FDPI in the mouse prefrontal cortical plasticity-related proteins and some parameters of toxicity. Adult Swiss mice were subjected to social defeat stress for 10 days. Two protocols with FDPI were carried out: 1- FDPI (25 mg/kg, intragastric) was administered to mice 24 h after the last social defeat stress episode; 2- FDPI (1-25 mg/kg, intragastric) was administered to mice once a day for 10 days concomitant with the social defeat stress...
June 30, 2017: Journal of Psychiatric Research
Yongdi Wang, Jinxu Liao, Shao-Jun Tang, Jianhong Shu, Wenping Zhang
HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway...
June 2017: Journal of Molecular Neuroscience: MN
Joon-Ki Park, Young-Pyo Hong, Sam-Jun Lee
Ovariectomy (OVX) is a method used to block estrogen in female rats that induces hippocampal dysfunction and affects brain‑derived neurotrophic factor (BDNF) pathways. The majority of previous studies investigating OVX focused on BDNF expression in the hippocampus and cognitive function. The present study focused on the pathways of each BDNF type, precursor (proBDNF) and mature (mBDNF), and the effects of regular exercise in the hippocampus of ovariectomized rats. Female Sprague‑Dawely rats were used and OVX surgery was performed...
July 2017: Molecular Medicine Reports
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