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https://www.readbyqxmd.com/read/28550793/acute-gonadotropin-releasing-hormone-agonist-treatment-enhances-extinction-memory-in-male-rats
#1
L Y Maeng, M B Taha, K K Cover, S S Glynn, M Murillo, K Lebron-Milad, M R Milad
Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known...
May 17, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28550642/post-heroin-dose-tissue-distribution-of-6-monoacetylmorphine-6-mam-with-maldi-imaging
#2
Belin G Teklezgi, Annapurna Pamreddy, Sooraj Baijnath, Nirmala D Gopal, Tricia Naicker, Hendrik G Kruger, Thavendran Govender
Heroin is an illicit opioid drug which is commonly abused and leads to dependence and addiction. Heroin is considered a pro-drug and is rapidly converted to its major active metabolite 6-monoacetylmorphine (6-MAM) which mediates euphoria and reward through the stimulation of opioid receptors in the brain. The aim of this study was to investigate the distribution and localization of 6-MAM in the healthy Sprague Dawley rat brain following intraperitoneal (i.p) administration of heroin (10 mg/kg), using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), in combination with quantification via liquid chromatography mass spectrometry (LC-MS/MS)...
May 26, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28550529/single-administration-of-hbk-15-a-triple-5-ht1a-5-ht7-and-5-ht3-receptor-antagonist-reverses-depressive-like-behaviors-in-mouse-model-of-depression-induced-by-corticosterone
#3
Karolina Pytka, Monika Głuch-Lutwin, Magdalena Kotańska, Anna Waszkielewicz, Agnieszka Kij, Maria Walczak
Studies suggest that the blockade of 5-HT1A, 5-HT7, and 5-HT3 receptor may increase the speed of antidepressant response. 1-[(2,6-Dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15), dual 5-HT1A and 5-HT7 antagonists, showed significant antidepressant- and anxiolytic-like properties in our previous tests in rodents. In this study, we aimed to investigate their antidepressant potential using mouse model of corticosterone-induced depression...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28550249/avn-492-a-novel-highly-selective-5-ht6r-antagonist-preclinical-evaluation
#4
Alexandre V Ivachtchenko, Ilya Okun, Vladimir Aladinskiy, Yan Ivanenkov, Angela Koryakova, Ruben Karapetyan, Oleg Mitkin, Ramiz Salimov, Andrey Ivashchenko
Discovery of 5-HT6 receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer's disease, schizophrenia, and obesity. In the present study, we present preclinical evaluation of a novel highly-potent and highly-selective 5-HT6R antagonist, AVN-492. The affinity of AVN-492 to bind to 5-HT6R (Ki = 91 pM) was more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki = 170 nM). Thus, the compound displayed great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550243/apomorphine-therapy-for-neuronal-insulin-resistance-in-a-mouse-model-of-alzheimer-s-disease
#5
Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T Yanagihara, Kyoko M Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira
Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550169/the-gliotransmitter-d-serine-promotes-synapse-maturation-and-axonal-stabilization-in-vivo
#6
Marion R Van Horn, Arielle Strasser, Lois S Miraucourt, Loredano Pollegioni, Edward S Ruthazer
The N-methyl-D-aspartate receptor (NMDAR) is thought to play a key role in the refinement of connectivity in developing neural circuits. Pharmacological blockade or genetic loss-of-function manipulations that prevent NMDAR function during development result in the disorganization of topographic axonal projections. However, because NMDARs contribute to overall glutamatergic neurotransmission, such loss-of-function experiments fail to adequately distinguish between the roles played by NMDARs and neural activity in general...
May 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28550144/exacerbation-of-oxygen-glucose-deprivation-induced-blood-brain-barrier-disruption-potential-pathogenic-role-of-interleukin-9-in-ischemic-stroke
#7
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu
Interleukin (IL) -9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke. We recruited 42 patients newly diagnosed with ischemic stroke and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals...
May 26, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13ralpha2-car-t-cells-but-results-in-antigen-loss-variants
#8
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CARs) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens such as IL13Ralpha2 (interleukin 13 Receptor Subunit Alpha 2), HER2 (human epidermal growth factor receptor 2), and EGFRvIII (epidermal growth factor receptor variant III) have had antitumor activity in preclinical models, early phase clinical testing has demonstrated limited antiglioma activity...
May 26, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28550025/mineralocorticoid-receptor-null-mice-informing-cell-type-specific-roles
#9
Timothy James Cole, Morag Young
The mineralocorticoid receptor (MR) mediates the actions of two important adrenal corticosteroid hormones, aldosterone and cortisol. The cell signalling roles of the MR in vivo have expanded enormously since the cloning of human MR gene 30 years ago and the first MR gene knockout in mice nearly 20 years ago. Complete ablation of the MR revealed important roles postnatally for regulation of kidney epithelial functions, with MR-null mice dying 1-2 weeks postnatally from renal salt wasting and hyperkalaemia, with elevated plasma renin and aldosterone...
May 26, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28549949/recent-advancements-in-liposomes-targeting-strategies-to-cross-blood-brain-barrier-bbb-for-the-treatment-of-alzheimer-s-disease
#10
REVIEW
Mukta Agrawal, Ajazuddin, Dulal K Tripathi, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Spyridon Mourtas, Margareta Hammarlund-Udenaes, Amit Alexander
In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli...
May 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28549890/-18-f-labeled-indole-based-analogs-as-highly-selective-radioligands-for-imaging-sigma-2-receptors-in-the-brain
#11
Liang Wang, Jiajun Ye, Yingfang He, Winnie Deuther-Conrad, Jinming Zhang, Xiaojun Zhang, Mengchao Cui, Jörg Steinbach, Yiyun Huang, Peter Brust, Hongmei Jia
We have designed and synthesized a series of indole-based σ2 receptor ligands containing 5,6-dimethoxyisoindoline or 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline as pharmacophore. In vitro competition binding assays showed that all ten ligands possessed low nanomolar affinity (Ki=1.79-5.23nM) for σ2 receptors and high subtype selectivity (Ki (σ2)/Ki (σ1)=56-708). Moreover, they showed high selectivity for σ2 receptor over the vesicular acetylcholine transporter (>1000-fold). The corresponding radiotracers [(18)F]16 and [(18)F]21 were prepared by an efficient one-pot, two-step reaction sequence with a home-made automated synthesis module, with 10-15% radiochemical yield and radiochemical purity of >99%...
May 10, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28549853/molecular-fingerprinting-of-principal-neurons-in-the-rodent-hippocampus-a-neuroinformatics-approach
#12
D J Hamilton, C M White, C L Rees, D W Wheeler, G A Ascoli
Neurons are often classified by their morphological and molecular properties. The online knowledge base Hippocampome.org primarily defines neuron types from the rodent hippocampal formation based on their main neurotransmitter (glutamate or GABA) and the spatial distributions of their axons and dendrites. For each neuron type, this open-access resource reports any and all published information regarding the presence or absence of known molecular markers, including calcium-binding proteins, neuropeptides, receptors, channels, transcription factors, and other molecules of biomedical relevance...
April 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28549782/central-trkb-blockade-attenuates-icv-angiotensin-ii-hypertension-and-sympathetic-nerve-activity-in-male-sprague-dawley-rats
#13
Bryan K Becker, Hanjun Wang, Irving H Zucker
Increased sympathetic nerve activity and the activation of the central renin-angiotensin system are commonly associated with cardiovascular disease states such as hypertension and heart failure, yet the precise mechanisms contributing to the long-term maintenance of this sympatho-excitation are incompletely understood. Due to the established physiological role of neurotrophins contributing toward neuroplasticity and neuronal excitability along with recent evidence linking the renin-angiotensin system and brain-derived neurotrophic factor (BDNF) along with its receptor (TrkB), it is likely the two systems interact to promote sympatho-excitation during cardiovascular disease...
May 19, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28548869/neurotransmitter-receptor-availability-in-the-rat-brain-is-constant-in-a-24-hour-period
#14
A Oskamp, F Wedekind, T Kroll, D Elmenhorst, A Bauer
Wakefulness and sleep are fundamental characteristics of the brain. We, therefore, hypothesized that transmitter systems contribute to their regulation and will exhibit circadian alterations. We assessed the concentration of various neurotransmitter receptors and transporters including adenosinergic (A1AR, A2AAR, and ENT1), dopaminergic (D1R, D2R, and DAT), and serotonergic (5-HT2AR) target proteins. Adult male Sprague Dawley rats were used and maintained in a 12 h light: 12 h dark cycle (lights on from 07:00 h to 19:00 h)...
May 26, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28547726/stroke-induces-mesenchymal-stem-cell-migration-to-infarcted-brain-areas-via-cxcr4-and-c-met-signaling
#15
Oh Young Bang, Gyeong Joon Moon, Dong Hee Kim, Ji Hyun Lee, Sooyoon Kim, Jeong Pyo Son, Yeon Hee Cho, Won Hyuk Chang, Yun-Hee Kim
Mesenchymal stem cells circulate between organs to repair and maintain tissues. Mesenchymal stem cells cultured with fetal bovine serum have therapeutic effects when intravenously administered after stroke. However, only a small number of mesenchymal stem cells reach the brain. We hypothesized that the serum from stroke patients increases mesenchymal stem cells trophism toward the infarcted brain area. Mesenchymal stem cells were grown in fetal bovine serum, normal serum from normal rats, or stroke serum from ischemic stroke rats...
May 25, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28547529/toll-like-receptor-4-tlr4-and-triggering-receptor-expressed-on-myeloid-cells-2-trem-2-activation-balance-astrocyte-polarization-into-a-proinflammatory-phenotype
#16
Gerardo Rosciszewski, Vanesa Cadena, Veronica Murta, Jeronimo Lukin, Alejandro Villarreal, Thierry Roger, Alberto Javier Ramos
Astrocytes react to brain injury with a generic response known as reactive gliosis, which involves activation of multiple intracellular pathways including several that may be beneficial for neuronal survival. However, by unknown mechanisms, reactive astrocytes can polarize into a proinflammatory phenotype that induces neurodegeneration. In order to study reactive gliosis and astroglial polarization into a proinflammatory phenotype, we used cortical devascularization-induced brain ischemia in Wistar rats and primary astroglial cell cultures exposed to oxygen-glucose deprivation (OGD)...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28546544/reproducing-infra-slow-oscillations-with-dopaminergic-modulation
#17
Toshihiro Kobayashi, Yutaka Shimada, Kantaro Fujiwara, Tohru Ikeguchi
In the human brain, billions of neurons construct a neural network via synaptic connections. Neuronal excitation and inhibition are transmitted to other neurons through synapses via neurotransmitters. Dopamine is one of these neurotransmitters that plays a number of important roles. There are a variety of rhythms in the brain, such as alpha rhythm, beta rhythm, and so on. Infra-slow oscillation, ISO, is one of the rhythms observed in the brain, and ranges below 0.1 Hz. One of the key roles of dopamine is the generation of ISO in neural networks...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546056/glutamate-in-dorsolateral-prefrontal-cortex-and-auditory-verbal-hallucinations-in-patients-with-schizophrenia-a-1-h-mrs-study
#18
Branislava Ćurčić-Blake, Leonie Bais, Anita Sibeijn-Kuiper, Marieke Pijnenborg, Henderikus Knegtering, Edith Liemburg, André Aleman
PURPOSE: Glutamatergic models of psychosis propose that dysfunction of N-methyl-d-aspartate (NMDA) receptors, and associated excess of glutamate, may underlie psychotic experiences in people with schizophrenia. However, little is known about the specific relation between glutamate and auditory verbal hallucinations (AVH) in patients with psychosis. In this study, levels of glutamate+glutamine (Glx) in the left lateral prefrontal lobe were determined using proton magnetic resonance spectroscopy ((1)H MRS) to calculate their association with AVH...
May 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28545898/risk-averse-personalities-have-a-systemically-potentiated-neuroendocrine-stress-axis-a-multilevel-experiment-in-parus-major
#19
Alexander T Baugh, Rebecca A Senft, Marian Firke, Abigail Lauder, Julia Schroeder, Simone L Meddle, Kees van Oers, Michaela Hau
Hormonal pleiotropy-the simultaneous influence of a single hormone on multiple traits-has been hypothesized as an important mechanism underlying personality, and circulating glucocorticoids are central to this idea. A major gap in our understanding is the neural basis for this link. Here we examine the stability and structure of behavioral, endocrine and neuroendocrine traits in a population of songbirds (Parus major). Upon identifying stable and covarying behavioral and endocrine traits, we test the hypothesis that risk-averse personalities exhibit a neuroendocrine stress axis that is systemically potentiated-characterized by stronger glucocorticoid reactivity and weaker negative feedback...
May 22, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28545672/enhancement-of-apoptotic-activities-on-brain-cancer-cells-via-the-combination-of-%C3%AE-tocotrienol-and-jerantinine-a
#20
Ibrahim Babangida Abubakar, Kuan-Hon Lim, Toh-Seok Kam, Hwei-San Loh
BACKGROUND: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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