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Masatake Fujimura, Fusako Usuki
Methylmercury (MeHg) induces site-specific cerebrocortical neuronal cell death. In our previous study using an in vivo mouse model, we reported that MeHg-induced cerebrocortical neuronal cell death may be due to neural hyperactivity triggered by activation of kinase pathways. However, the detailed molecular mechanism remained to be completely understood. In this study, we analyzed detailed signaling pathways for MeHg-induced neuronal cell death using all-trans-retinoic acid (RA) differentiated SH-SY5Y cells, which show neuron-like morphological changes and express neuron/synapse markers for cerebrocortical neurons...
June 15, 2018: Neurotoxicology
Zhe Zhao, Haitao Wu
Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for various neurological and psychiatric disorders. HFS in the deep region of the brain, also named deep-brain stimulation (DBS), is becoming increasingly important in clinical trials. Recent progress in the field of high-frequency DBS (HF-DBS) surgery has begun to spread the possibility of utilizing this invasive technique to other situations, such as treatment for major depression disorder (MDD), obsessive-compulsive disorder (OCD), and so on...
June 2, 2018: Journal of Visualized Experiments: JoVE
María Banqueri, Marta Méndez, Jorge L Arias
Subjects' early life events will affect them later in life. When these events are stressful, such as child abuse in humans or repeated maternal separation in rodents, subjects can show some behavioral and brain alterations. This study used young adult female Wistar rats that were maternally raised (AFR), maternally separated from post-natal day (PND) 1 to PND10 (MS10), or maternally separated from PND1 to PND21 (MS21), in order to assess the effects of maternal separation (MS) on spatial learning and memory, as well as cognitive flexibility, using the Morris Water Maze (MWM)...
June 14, 2018: Neurobiology of Learning and Memory
Sanjay Singh, Sarfraj Ahmad Siddiqui, Sukanya Tripathy, Shiv Kumar, Sudipta Saha, Rajesh Ugale, Dinesh Raj Modi, Anand Prakash
In the last few decades, there has been exponential increase in studies aiming to trace the molecular mechanism of fear extinction with a hope to minimize the return of fear after exposure therapy required for operational treatment of anxiety disorders. The present study explored how the timing of extinction training after developing a specific fear, affects the consequent return of the extinguished fear and the role of histone acetylation in controlling the circuitry, thereof. It was found that rats undergone extinction training 10 min...
June 14, 2018: Brain Research Bulletin
Hari Madhuri Doss, Snigdha Samarpita, Ramamoorthi Ganesan, Mahaboobkhan Rasool
AIMS: Bone erosion induced by enhanced osteoclast formation is a debilitating pathological phenomenon in rheumatoid arthritis (RA). Recent finding has revealed that ferulic acid is associated with reduced osteoclast differentiation and bone erosion. However, the underlying mechanism through which ferulic acid inhibited osteoclast differentiation and bone erosion still remains to be elucidated. This study assessed the therapeutic effects of ferulic acid on osteoclast differentiation and bone erosion by targeting RANKL dependent NF-κB pathway...
June 14, 2018: Life Sciences
Takaaki Noguchi, Kosuke Ebina, Makoto Hirao, Satoru Otsuru, Adam J Guess, Ryota Kawase, Tohru Ohama, Shizuya Yamashita, Yuki Etani, Gensuke Okamura, Hideki Yoshikawa
Apolipoprotein E (ApoE) plays crucial roles not only in lipid metabolism but also in bone metabolism. Specifically ApoE4, one of major ApoE isoforms, has been demonstrated to be associated with increased risk of developing osteoporosis compared to another major isoform ApoE3. However, the detailed mechanism of how the different ApoE isoforms affect bone metabolism remains unclear. Micro-CT analyses of distal femora demonstrated severely decreased bone mass in 48-week-old female homozygous ApoE-knockout (ApoE-KO) mice compared to age- and gender-matched wild type C57BL/6 J (WT) mice...
June 12, 2018: Biochemical and Biophysical Research Communications
Yasuyuki Fujii, Kenta Suzuki, Yahiro Hasegawa, Fumio Nanba, Toshiya Toda, Takahiro Adachi, Shu Taira, Naomi Osakabe
We previously confirmed that postprandial alterations in the circulation and metabolism after a single oral dose of flavan 3-ols (mixture of catechin and catechin oligomers) were involved in an increase in sympathetic nervous activity. However, it is well known that, in response to various stresses, activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs together with sympathetic nerve activity, which is associated with activation of the sympathetic-adrenal-medullary (SAM) axis. In this study, we examined whether the HPA axis was activated after a single dose of flavan 3-ols...
June 11, 2018: Neuroscience Letters
Fei-Fei Li, Bo Zhang, Ji-Hong Cui, Fu-Lin Chen, Yin Ding, Xue Feng
Mechanical load application promotes bone formation, while reduced load leads to bone loss. However, the underlying mechanisms that regulate new bone formation are not fully understood. Wnt/β‑catenin signaling has an important role in bone formation, bone growth and remodeling. The aim of the present study was to investigate whether mechanical stimuli regulated bone formation through the Wnt/β‑catenin signaling pathway. Saos‑2 osteoblastic cells were subjected to mechanical strain using a Flexcell strain loading system...
June 7, 2018: Molecular Medicine Reports
Wei Liu, Wen Wu, Guangyong Lin, Jian Cheng, Yanyan Zeng, Yu Shi
Physical exercise is beneficial for the functional recovery of neurons after stroke. It has been suggested that exercise regulates proliferation and differentiation of endogenous neural stem cells (NSCs); however, the underlying molecular mechanisms are still largely unknown. In the present study, the aim was to investigate whether physical exercise activates the extracellular signal‑regulated kinase (ERK) signaling pathway to promote proliferation and differentiation of NSCs in rats with cerebral infarction, thereby improving neurological function...
June 7, 2018: Molecular Medicine Reports
Despina E Ganella, Ly Dao Nguyen, Luba Lee-Kardashyan, Leah E Kim, Antonio G Paolini, Jee Hyun Kim
In contrast to adult rodents, juvenile rodents fail to show relapse following extinction of conditioned fear. Using different retrograde tracers injected into the infralimbic cortex (IL) and the ventral hippocampus (vHPC) in conjunction with c-Fos and parvalbumin (PV) immunochemistry, we investigated the neurocircuitry of extinction in juvenile and adult rats. Regardless of fear extinction or retrieval, juvenile rats had more c-Fos+ neurons in the basolateral amygdala (BLA) compared to adults, and showed a higher proportion of c-Fos+ IL-projecting neurons...
June 10, 2018: Behavioural Brain Research
Evert Njomen, Pawel A Osmulski, Corey L Jones, Maria E Gaczynska, Jetze J Tepe
The 20S proteasome is the main protease that directly targets intrinsically disordered proteins (IDPs) for proteolytic degradation. Mutations, oxidative stress or aging can induce the build-up of IDPs result-ing in incorrect signaling or aggregation, associated with the pathogenesis of many cancers and neuro-degenerative diseases. Drugs that facilitate 20S-mediated proteolysis have therefore many potential therapeutic applications. We report herein the modulation of proteasome assembly by the small mole-cule TCH-165, resulting in an increase in 20S levels...
June 13, 2018: Biochemistry
Ni Zhang, Liang Yang, Lanting Guo, Sheng Bi
Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified the action of neuronal activation in the dorsomedial hypothalamus (DMH) in modulating physical activity, food intake and body weight using leptin receptor mutant obese Zucker ( Lepr(fa) , ZF) and Koletsky ( Lepr(fak) , SHROB) rats...
2018: Frontiers in Molecular Neuroscience
Akash H Verma, Hanna Zafar, Nicole O Ponde, Olivia W Hepworth, Diksha Sihra, Felix E Y Aggor, Joseph S Ainscough, Jemima Ho, Jonathan P Richardson, Bianca M Coleman, Bernhard Hube, Martin Stacey, Mandy J McGeachy, Julian R Naglik, Sarah L Gaffen, David L Moyes
Protection against microbial infection by the induction of inflammation is a key function of the IL-1 superfamily, including both classical IL-1 and the new IL-36 cytokine families. Candida albicans is a frequent human fungal pathogen causing mucosal infections. Although the initiators and effectors important in protective host responses to C. albicans are well described, the key players in driving these responses remain poorly defined. Recent work has identified a central role played by IL-1 in inducing innate Type-17 immune responses to clear C...
June 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Katja Lingelbach, Arian Hach, Rick E Bernardi, Rainer Spanagel, Hilmar Bading, C Peter Bengtson
Despite the reduced life expectancy and staggering financial burden of medical treatment associated with tobacco smoking, the molecular, cellular and ensemble adaptations associated with chronic nicotine consumption remain poorly understood. Complex circuitry interconnecting dopaminergic and cholinergic regions of the midbrain and mesopontine tegmentum are critical for nicotine associated reward. Yet our knowledge of the nicotine activation of these regions is incomplete, in part due to their cell type diversity...
June 11, 2018: Journal of Comparative Neurology
Giorgio Bergamini, Jonas Mechtersheimer, Damiano Azzinnari, Hannes Sigrist, Michaela Buerge, Robert Dallmann, Robert Freije, Afroditi Kouraki, Jolanta Opacka-Juffry, Erich Seifritz, Boris Ferger, Tobias Suter, Christopher R Pryce
Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA) neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states...
February 2018: Neurobiology of Stress
Young-Jin Kim, Ji Young Lee, Hyun-Ju Kim, Do-Hoon Kim, Tae Hee Lee, Mi Suk Kang, Wansu Park
The dry root of Angelica sinensis (Oliv.) Diels, also known as “female ginseng”, is a popular herbal drug amongst women, used to treat a variety of health issues and cardiovascular diseases. The aim of this study is to evaluate the detailed molecular mechanism for anti-inflammatory effects of Angelica sinensis root water extract (ASW). The anti-inflammatory effect of ASW on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages was evaluated by the tetrazolium-based colorimetric assay (MTT), Griess reagent assay, multiplex cytokine assay, real time reverse transcription polymerase chain reaction (RT-PCR), and Fluo-4 calcium assay...
May 21, 2018: Nutrients
Ke Zhang, Jun Lei, Yuan He, Xiaobin Yang, Zhen Zhang, Dingjun Hao, Biao Wang, Baorong He
Function studies of pectolinarigenin demonstrated that, as a natural product, it possesses the regulatory effects on transcription factors (TFs) such as: signal transducer and activator of transcription 3 (STAT3). Herein, we aimed to identify the regulatroy effects of pectolinarigenin on the osteoclastogenesis TFs such as: NFATc1 and c-Fos, and further identify the relevant up-stream signals activity. We initially found pectolinarigenin inhibited receptor activator of nuclear factor-kappa B ligand (RANKL) induced osteoclast formation during the bone marrow-derived macrophages (BMMs) cultures, suggesting that this natural product could act on osteoclast precursors by inhibiting the down signaling cascades of RANKL signaling...
June 4, 2018: International Immunopharmacology
Catherine Chaumontet, Isidra Recio, Gilles Fromentin, Simon Benoit, Julien Piedcoq, Nicolas Darcel, Daniel Tomé
Background: Protein status is controlled by the brain, which modulates feeding behavior to prevent protein deficiency. Objective: This study tested in rats whether protein status modulates feeding behavior through brain reward pathways. Methods: Experiments were conducted in male Wistar rats (mean ± SD weight; 230 ± 16 g). In experiment 1, rats adapted for 2 wk to a low-protein (LP; 6% of energy) or a normal-protein (NP; 14% of energy) diet were offered a choice between 3 cups containing high-protein (HP; 50% of energy), NP, or LP feed; their intake was measured for 24 h...
June 1, 2018: Journal of Nutrition
A Merchán, S Mora, B Gago, E Rodriguez-Ortega, A Fernández-Teruel, J López Puga, F Sánchez-Santed, M Moreno, P Flores
Schedule-induced polydipsia (SIP) is an animal model of compulsive drinking that selects for individual differences and varies across rat strains. The aim of this study was to investigate excessive habit formation by analyzing the SIP licking microstructure among rat strains, and to compare the brain areas activated by SIP in different populations. Wistar, Long Evans, and Roman High- and Low-Avoidance rat strains were compared using a cluster analysis of two main variables, i.e., frequency of licking (percentage of inter-pellet intervals with drinking episodes) and intensity of licking (mean number of licks per inter-pellet interval), and were found to exhibit high intensity and frequent licking (Compulsive Drinkers; CD), low intensity but frequent licking (Habitual Drinkers; HD), and low intensity and low frequency licking (Low Drinkers; LD)...
June 7, 2018: Genes, Brain, and Behavior
Ai-Jun Li, Qing Wang, Sue Ritter
Catecholamine (CA) neurons within the A1 and C1 cell groups in the ventrolateral medulla (VLM) potently increase food intake when activated by glucose deficit. In contrast, CA neurons in the A2 cell group of the dorsomedial medulla are required for reduction of food intake by cholecystokinin (CCK), a peptide that promotes satiation. Thus, dorsal and ventral medullary CA neurons are activated by divergent metabolic conditions and mediate opposing behavioral responses. Acute glucose deficit is a life-threatening condition, and increased feeding is a key response that facilitates survival of this emergency...
June 6, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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