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Cushla R McCarthny, Xin Du, YeeWen Candace Wu, Rachel A Hill
Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF). This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/- ) on hippocampal NMDA-R expression. Wild-type and BDNF+/- mice were gonadectomised, and females received either 17 β -estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT) treatment. Dorsal (DHP) and ventral hippocampus (VHP) were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis...
2018: International Journal of Endocrinology
Michelle T Tong, Tae-Young P Kim, Thomas A Cleland
Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB...
May 2018: Learning & Memory
Julie K Allen, Guillermo N Armaiz-Pena, Archana S Nagaraja, Nouara C Sadaoui, Tatiana Ortiz, Robert Dood, Merve Ozcan, Danielle M Herder, Monika Haemerrle, Kshipra M Gharpure, Rajesha Rupaimoole, Rebecca Previs, Sherry Y Wu, Sunila Pradeep, Xiaoyun Xu, Hee Dong Han, Behrouz Zand, Heather J Dalton, Morgan Taylor, Wei Hu, Justin Bottsford-Miller, Myrthala Moreno-Smith, Yu Kang, Lingegowda S Mangala, Cristian Rodriguez-Aguayo, Vasudha Sehgal, Erika L Spaeth, Prahlad T Ram, Stephen Tc Wong, Frank C Marini, Gabriel Lopez-Berestein, Steve W Cole, Susan K Lutgendorf, Mariella diBiasi, Anil K Sood
Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present evidence for a feedforward loop whereby adrenergic signaling leads to increased tumoral innervation. In response to catecholamines, tumor cells produced brain-derived neurotrophic factor (BDNF) in an ADRB3/cAMP/Epac/JNK-dependent manner...
April 16, 2018: Cancer Research
R U Ostrovskaya, S S Yagubova, T A Gudasheva, S B Seredenin
Reduced proliferation and enhanced apoptosis of β cells in diabetes mellitus are associated with a deficiency of brain-derived neurotrophic factor (BDNF). Low-molecular weight compounds similar to different BDNF loops were synthesized at the V. V. Zakusov Research Institute of Pharmacology. They produce a potentiating effect on TrkB phosphorylation, but differently activate post-receptor signaling pathways. We compared their effects on the severity of streptozotocin-induced diabetes mellitus in C57Bl/6 mice...
April 16, 2018: Bulletin of Experimental Biology and Medicine
Cassiano R A F Diniz, Plinio C Casarotto, Leonardo Resstel, R L Joca Sâmia
Depression and posttraumatic stress disorder are assumed to be maladaptive responses to stress and antidepressants are thought to counteract such responses by increasing BDNF (brain-derived neurotrophic factor) levels. BDNF acts through TrkB (tropomyosin-related receptor kinase B) and plays a central role in neuroplasticity. In contrast, both precursor proBDNF and BDNF propeptide (another metabolic product from proBDNF cleavage) have a high affinity to p75 receptor (p75R) and usually convey apoptosis and neuronal shrinkage...
April 4, 2018: Neuroscience and Biobehavioral Reviews
Junfei Zhou, Fang Wang, Jun Zhang, Jianfeng Li, Li Ma, Tieli Dong, Zhigang Zhuang
BACKGROUND: The aim of the present study was to verify whether propofol impaired learning and memory through the interplay of N-methyl-D-aspartate (NMDA) receptor with brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway. METHODS: 120 Sprague-Dawley (SD) rats were randomly assigned into eight groups. Experimental drugs including saline, intralipid, propofol, N-methyl-D-aspartate (NMDA), 7,8-dihydroxyflavone (7,8-DHF), K252a and MK-801...
April 5, 2018: BMC Anesthesiology
Allison M Lange, Hui-Wen Lo
Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular region stimulating dimerization, phosphorylation, and activation of downstream signaling pathways...
April 4, 2018: Cancers
Robert M Dietz, James E Orfila, Krista M Rodgers, Olivia P Patsos, Guiying Deng, Nicholas Chalmers, Nidia Quillinan, Richard J Traystman, Paco S Herson
Global ischemia in childhood often leads to poor neurologic outcomes, including learning and memory deficits. Using our novel model of childhood cardiac arrest/cardiopulmonary resuscitation (CA/CPR), we investigate the mechanism of ischemia-induced cognitive deficits and recovery. Memory is impaired seven days after juvenile CA/CPR and completely recovers by 30 days. Consistent with this remarkable recovery not observed in adults, hippocampal long-term potentiation (LTP) is impaired 7-14 days after CA/CPR, recovering by 30 days...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Michaela Shishmanova-Doseva, Lyudmil Peychev, Yvetta Koeva, Dora Terzieva, Katerina Georgieva, Zhivko Peychev
Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide - 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30)...
March 29, 2018: Pharmacology, Biochemistry, and Behavior
Jin Liu, Fatou Amar, Carlo Corona, Raphaella W L So, Stuart J Andrews, Peter L Nagy, Michael L Shelanski, Lloyd A Greene
Activating transcription factor 4 (ATF4) plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF) promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB) signaling, but independent of levels of phosphorylated eIF2α...
2018: Frontiers in Molecular Neuroscience
Makoto Kawamoto, Keigo Ozono, Yasuhiro Oyama, Akio Yamasaki, Yoshinao Oda, Hideya Onishi
We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors...
April 2018: Anticancer Research
Pascale Bouchard-Cannon, Christopher Lowden, Dennison Trinh, Hai-Ying M Cheng
Adult hippocampal neurogenesis is highly responsive to exercise, which promotes the proliferation of neural progenitor cells and the integration of newborn granule neurons in the dentate gyrus. Here we show that genetic ablation of the small GTPase, Dexras1, suppresses exercise-induced proliferation of neural progenitors, alters survival of mitotic and post-mitotic cells in a stage-specific manner, and increases the number of mature newborn granule neurons. Dexras1 is required for exercise-triggered recruitment of quiescent neural progenitors into the cell cycle...
March 28, 2018: Scientific Reports
Daniel Richard Gomez, Lauren Averett Byers, Monique Nilsson, Lixia Diao, Jing Wang, Lerong Li, Pan Tong, Mia Hofstad, Babita Saigal, Ignacio Wistuba, Neda Kalhor, Stephen Swisher, Youhong Fan, Waun Ki Hong, Milind Suraokar, Carmen Behrens, Cesar Moran, John Victor Heymach
While several molecular targets have been identified for adenocarcinoma (ACA) of the lung, similar drivers with squamous cell carcinoma (SCC) are sparse. We compared signaling pathways and potential therapeutic targets in lung SCC and ACA tumors using reverse phase proteomic arrays (RPPA) from two independent cohorts of resected early stage NSCLC patients: a testing set using an MDACC cohort (N=140) and a validation set using the Cancer Genome Atlas (TCGA) cohorts. We identified multiple potentially targetable proteins upregulated in SCC, including NRF2, Keap1, PARP, TrkB, and Chk2...
March 6, 2018: Oncotarget
Eros Quarta, Gianluca Fulgenzi, Riccardo Bravi, Erez James Cohen, Sudhirkumar Yanpallewar, Lino Tessarollo, Diego Minciacchi
Amyotrophic lateral sclerosis (ALS) causes rapidly progressive paralysis and death within 5 years from diagnosis due to degeneration of the motor circuits. However, a significant population of ALS patients also shows cognitive impairments and progressive hippocampal pathology. Likewise, the mutant SOD1(G93A) mouse model of ALS (mSOD1), in addition to loss of spinal motor neurons, displays altered spatial behavior and hippocampal abnormalities including loss of parvalbumin-positive interneurons (PVi) and enhanced long-term potentiation (LTP)...
March 23, 2018: Molecular and Cellular Neurosciences
Yong-Ping Zhang, Hao-Yin Wang, Cai Zhang, Bai-Ping Liu, Zhi-Lan Peng, Yu-Yu Li, Cai Song
Increased proinflammatory cytokines, such as interleukin (IL)-1β, may play an important role in the etiology of depression because they cause the hypothalamic-pituitary-adrenal axis to release glucocorticoids (GC) and induce dysfunction of serotonin and norepinephrine neurotransmission. Sustained increase in GC may activate microglia to induce neuroinflammation, and suppress astrocytes to produce neurotrophins, which lead to neuronal apoptosis. Here, we tested the hypothesis that glucocorticoid receptor (GR) antagonist mifepristone (RU486) may attenuate IL-1β-induced depression-like behavior by regulating the neuroinflammation and neurotrophin functions of microglia and astrocytes...
March 23, 2018: Behavioural Brain Research
Wei Guo, Guhan Nagappan, Bai Lu
Brain-derived neurotrophic factor (BDNF) serves a pleiotropic role in the central nervous system, ranging from promoting neuronal survival and differentiation during development and synaptic modulation in the adult. An important yet unanswered question is how BDNF could serve such diverse functions, sometimes in the same cell. At least two modes of BDNF actions have been elucidated so far based on BDNF signaling kinetics and/or the activity status of the responding neurons. Acute and gradual increases in extracellular BDNF concentrations elicit, respectively, transient and sustained activation of TrkB receptor and its downstream signaling, leading to differential molecular and cellular functions...
March 25, 2018: Developmental Neurobiology
Willy Chou, Yu-Fan Liu, Cheng-Hsien Lin, Mao-Tsun Lin, Chi-Chun Chen, Wen-Pin Liu, Ching-Ping Chang, Chung-Ching Chio
Physical exercise (PE) is an effective method for improving cognitive function among patients with traumatic brain injury (TBI). We previously demonstrated that PE with an infrared-sensing running wheel (ISRW) system provides strong neuroprotection in an experimental animal model of stroke. In this study, we used fluid percussion injury in rats to simulate mild TBI. For rats, we used both passive avoidance learning and the Y-maze tests to evaluate cognitive function. We investigated whether PE rehabilitation attenuated cognitive deficits in rats with TBI and determined the contribution of hippocampal and cortical expression of heat shock protein 20 (HSP20) to PE-mediated cognitive recovery...
March 25, 2018: Molecular Neurobiology
Irene Cheng, Lucy Jin, Lucy C Rose, Christopher D Deppmann
The peripheral somatosensory system overproduces neurons early in development followed by a period of cell death during final target innervation. The decision to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is mediated by target derived neurotrophic factors and their cognate receptors. Subsets of peripheral somatosensory neurons can be crudely defined by the neurotrophic receptors that they express: peptidergic nociceptors (TrkA+), non-peptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and proprioceptors (TrkC+)...
March 22, 2018: Developmental Neurobiology
Wen-Zhan Tu, Si-Si Li, Xia Jiang, Xin-Ru Qian, Guan-Hu Yang, Peng-Peng Gu, Bin Lu, Song-He Jiang
Microglia, which comprise a sensor for pathological events in the central nervous system, may be triggered by nerve injury and transformed from a quiescent state into an activated state; ionised calcium binding adaptor molecule 1 (Iba1) is a sensitive marker associated with activated microglia. Accumulated evidence suggests that spinal activated microglia and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signalling pathway play major roles in the production and development of neuropathic pain...
March 13, 2018: International Journal of Molecular Medicine
Kate M O'Neill, Katherine E Donohue, Anton Omelchenko, Bonnie L Firestein
The patterning of dendrites is regulated by many factors, such as brain-derived neurotrophic factor (BDNF), which our laboratory has previously shown alters the dendritic arbor uniquely depending on the mode of extracellular application. In the current work, we examine how BDNF affects dendritogenesis in hippocampal neurons when it is overexpressed intracellularly by transcripts previously reported to be transported to distinct cellular compartments. The BDNF gene is processed at two different polyadenylation sites, leading to mRNA transcription with two different length 3' untranslated regions (UTRs), and therefore, different mRNA localization preferences...
2018: Frontiers in Cellular Neuroscience
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