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Fabiana K Ludka, Maurício P Cunha, Tharine Dal-Cim, Luisa Bandeira Binder, Leandra C Constantino, Caio M Massari, Wagner C Martins, Ana Lúcia S Rodrigues, Carla I Tasca
Intracerebroventricular (icv) amyloid-beta (Aβ)1-40 infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ1-40 infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ1-40-induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice...
October 5, 2016: Molecular Neurobiology
Guoqing Zhao, Chen Zhang, Jun Chen, Yousong Su, Rubai Zhou, Fan Wang, Weiping Xia, Jia Huang, Zuowei Wang, Yingyan Hu, Lan Cao, Xiaoyun Guo, Chengmei Yuan, Yong Wang, Zhenghui Yi, Weihong Lu, Yan Wu, Zhiguo Wu, Wu Hong, Daihui Peng, Yiru Fang
There is a high rate of misdiagnosis between major depressive disorder (MDD) and bipolar disorder (BD) in clinical practice. Our previous work provided suggestive evidence for brain-derived neurotrophic factor (BDNF) in differentiating BD from MDD. In this study, we aimed to investigate the role of mature BDNF (mBDNF) and its precursor (proBDNF) in distinguishing bipolar depression (BP) from MDD during acute depressive episode. A total of 105 participants, including 44 healthy controls, 37 MDD patients and 24 BP patients, were recruited...
September 9, 2016: Molecular Neurobiology
You-Quan Ding, Xuan-Yang Li, Guan-Nan Xia, Hong-Yi Ren, Xin-Fu Zhou, Bing-Yin Su, Jian-Guo Qi
Schwann cell migration, including collective migration and chemotaxis, is essential for the formation of coordinate interactions between Schwann cells and axons during peripheral nerve development and regeneration. Moreover, limited migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes intermingling and spinal cord repair after Schwann cell transplantation into injured spinal cords. Recent studies have shown that mature brain-derived neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell migration...
October 2016: Tissue & Cell
Andres Stucky, Kalindi P Bakshi, Eitan Friedman, Hoau-Yan Wang
Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor-NR1 subunit as well as proBDNF and BDNF...
2016: PloS One
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
Li-Li Zeng, Xiao-Song He, Jian-Rong Liu, Chao-Bo Zheng, Yong-Ting Wang, Guo-Yuan Yang
AIMS: MicroRNAs play an important role in the pathogenesis of ischemic brain injury and in the repair process during postischemic condition. However, the key miRNAs and their function in these processes remain unclear. METHODS: Circulating blood MicroRNAs profiles were examined in the ischemic stroke patients. The predicted network of difference was analyzed by ingenuity pathway analysis. The key MicroRNAs were selected, and the function was further studied in a mouse ischemia model...
July 8, 2016: CNS Neuroscience & Therapeutics
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
J Guo, Y Ji, Y Ding, W Jiang, Y Sun, B Lu, G Nagappan
The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide, suggesting activity-dependent regulation of its extracellular levels...
2016: Cell Death & Disease
Hayat Banoujaafar, Alice Monnier, Nicolas Pernet, Aurore Quirié, Philippe Garnier, Anne Prigent-Tessier, Christine Marie
Scientific evidence continues to demonstrate a link between endothelial function and cognition. Besides, several studies have identified a complex interplay between nitric oxide (NO) and brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition. Therefore, this study investigated the link between cerebral endothelium-derived NO and BDNF signaling. For this purpose, levels of BDNF and the phosphorylated form of endothelial NO synthase at serine 1177 (p-eNOS) were simultaneously measured in the cortex and hippocampus of rats subjected to either bilateral common carotid occlusion (n = 6), physical exercise (n = 6) or a combination of both (n = 6) as experimental approaches to modulate flow-induced NO production by the cerebrovasculature...
September 2016: European Journal of Neuroscience
A A Borodinova, S V Salozhin
Brain-derived neurotrophic factor (BDNF) is one of the major protein regulators of diverse biological functions in the nervous system. It is synthesized as a precursor protein (proBDNF) that undergoes proteolytic cleavage in order to become a mature molecule. It was repeatedly shown that the proBDNF/ mBDNF ratio is determined by concomitant neuronal activity. A growing body of evidence argues that proBDNF has its own biological functions, oftentimes in opposition to functions of the mature molecule. Therefore, the balance of concentrations of proBDNF and mature neurotrophin is an important constituent of in any biological processes in nerve cells...
January 2016: Zhurnal Vyssheĭ Nervnoĭ Deiatelnosti Imeni I P Pavlova
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
Monika Wilkosc, Anita Markowska, Ludmila Zajac-Lamparska, Maria Skibinska, Agnieszka Szalkowska, Aleksander Araszkiewicz
Brain derived neurotrophic factor (BDNF) is considered to be connected with memory and learning through the processes of long term synaptic potentiation and synaptic plasticity. The aim of the study was to examine the relationship between precursor BDNF (proBNDF) and mature BDNF (mBDNF) serum levels and performance on Rey Auditory-Verbal Learning Test (RAVLT) in 150 healthy volunteers. In addition, we have verified the relationships between serum concentration of both forms of BDNF and RAVLT with sociodemographic and lifestyle factors...
2016: Frontiers in Neural Circuits
Ming Cai, Hong Wang, Jing-Jing Li, Yun-Li Zhang, Lei Xin, Feng Li, Shu-Jie Lou
High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models...
October 2016: Brain, Behavior, and Immunity
Rocío Beatriz Foltran, Silvina Laura Diaz
The brain-derived neurotrophic factor, BDNF, was discovered more than 30 years ago and, like other members of the neurotrophin family, this neuropeptide is synthetized as a proneurotrophin, the pro-BDNF, which is further cleaved to yield mature BDNF. The myriad of actions of these two BDNF isoforms in the central nervous system is constantly increasing and requires the development of sophisticated tools and animal models to refine our understanding. This review is focused on BDNF isoforms, their participation in the process of neurogenesis taking place in the hippocampus of adult mammals, and the modulation of their expression by serotonergic agents...
July 2016: Journal of Neurochemistry
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
Yoni Genzer, Maayan Dadon, Chen Burg, Nava Chapnik, Oren Froy
Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the brain and its decreased levels are associated with the development of obesity and neurodegeneration. Our aim was to test the effect of dietary fat, its timing and the circadian clock on the expression of BDNF and associated signaling pathways in mouse brain and liver. Bdnf mRNA oscillated robustly in brain and liver, but with a 12-h shift between the tissues. Brain and liver Bdnf mRNA showed a 12-h phase shift when fed ketogenic diet (KD) compared with high-fat diet (HFD) or low-fat diet (LFD)...
July 15, 2016: Molecular and Cellular Endocrinology
Bangkun Yang, Chun Yang, Qian Ren, Ji-Chun Zhang, Qian-Xue Chen, Yukihiko Shirayama, Kenji Hashimoto
Using learned helplessness (LH) model of depression, we measured protein expression of brain-derived neurotrophic factor (BDNF) pro-peptide, BDNF precursors (proBDNF and preproBDNF) in the brain regions of LH (susceptible) and non-LH rats (resilience). Expression of preproBDNF, proBDNF and BDNF pro-peptide in the medial prefrontal cortex of LH rats, but not non-LH rats, was significantly higher than control rats, although expression of these proteins in the nucleus accumbens of LH rats was significantly lower than control rats...
April 19, 2016: European Archives of Psychiatry and Clinical Neuroscience
Ajay X Thomas, Yasmin Cruz Del Angel, Marco I Gonzalez, Andrew J Carrel, Jessica Carlsen, Philip M Lam, Barbara L Hempstead, Shelley J Russek, Amy R Brooks-Kayal
Brain-derived neurotrophic factor (BDNF) levels are elevated after status epilepticus (SE), leading to activation of multiple signaling pathways, including the janus kinase/signal transducer and activator of transcription pathway that mediates a decrease in GABAA receptor α1 subunits in the hippocampus (Lund et al., 2008). While BDNF can signal via its pro or mature form, the relative contribution of these forms to signaling after SE is not fully known. In the current study, we investigate changes in proBDNF levels acutely after SE in C57BL/6J mice...
January 2016: ENeuro
Ana Paula Pesarico, Gláubia Sartori, César A Brüning, Anderson C Mantovani, Thiago Duarte, Gilson Zeni, Cristina Wayne Nogueira
Chronic unpredictable mild stress (CUMS) elicits aspects of cognitive and behavioral alterations that can be used to model comparable aspects of depression in humans. The aim of the present study was to investigate the antidepressant-like potential of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a novel isoquinoline compound, in CUMS, a model that meets face, construct and predictive criteria for validity. Swiss mice were subjected to different stress paradigms daily for a period of 35 days to induce the depressive-like behavior...
July 1, 2016: Behavioural Brain Research
Fan Zhang, Jie Luo, Su Min, Li Ren, Peipei Qin
This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear...
March 23, 2016: Brain Research
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