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https://www.readbyqxmd.com/read/28630404/activation-of-d1r-pka-mtor-signaling-cascade-in-medial-prefrontal-cortex-underlying-the-antidepressant-effects-of-l-spd
#1
Bing Zhang, Fei Guo, Yuqin Ma, Yingcai Song, Rong Lin, Fu-Yi Shen, Guo-Zhang Jin, Yang Li, Zhi-Qiang Liu
Major depressive disorder (MDD) is a common neuropsychiatric disorder characterized by diverse symptoms. Although several antidepressants can influence dopamine system in the medial prefrontal cortex (mPFC), but the role of D1R or D2R subtypes of dopamine receptor during anti-depression process is still vague in PFC region. To address this question, we investigate the antidepressant effect of levo-stepholidine (l-SPD), an antipsychotic medication with unique pharmacological profile of D1R agonism and D2R antagonism, and clarified its molecular mechanisms in the mPFC...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625767/early-life-stress-perturbs-the-function-of-microglia-in-the-developing-rodent-brain-new-insights-and-future-challenges
#2
REVIEW
Frances K Johnson, Arie Kaffman
The role of the innate immune system in mediating some of the consequences of childhood abuse and neglect has received increasing attention in recent years. Most of the work to date has focused on the role that neuroinflammation plays in the long-term adult psychiatric and medical complications associated with childhood maltreatment. The effects of stress-induced neuroinflammation on neurodevelopment have received little attention because until recently this issue has not been studied systematically in animal models of early life stress...
June 15, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28625569/synaptic-dysfunction-in-alzheimer-s-disease-from-the-role-of-amyloid-%C3%AE-peptide-to-the-%C3%AE-secretase-adam10
#3
Stefano Musardo, Elena Marcello
Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on patients, caregivers and society, it represents the largest unmet medical need in neurology, because it is currently incurable. In the last few years, the amyloid hypothesis, which points to amyloid β-peptide (Aβ) as the initiating factor in AD, had a central role in the development of therapeutic strategies for AD...
June 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28605546/plasticity-related-gene-expression-during-eszopiclone-induced-sleep
#4
Dmitry Gerashchenko, Ravi K Pasumarthi, Thomas S Kilduff
Study Objectives: Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. Methods: We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and 2 miRNAs critically involved in synaptic plasticity in these mice...
June 12, 2017: Sleep
https://www.readbyqxmd.com/read/28597477/effective-expression-of-drebrin-in-hippocampus-improves-cognitive-function-and-alleviates-lesions-of-alzheimer-s-disease-in-app-swe-ps1-%C3%AE-e9-mice
#5
Yan Liu, Yan-Feng Xu, Ling Zhang, Lan Huang, Pin Yu, Hua Zhu, Wei Deng, Chuan Qin
AIMS: Alzheimer's disease (AD), a progressive development dementia, is increasingly impacting patients' living conditions worldwide. Despite medical care and funding support, there are still no highly individualized drugs and practical strategies for clinical prevention and treatment. Developmentally regulated brain protein (abbreviated as Drebrin or Dbn, also known as Dbn1 in mouse) exists in neurons, especially in dendrites, and is an actin-binding protein that modulates synaptic morphology and long-term memory...
July 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28589176/arhgef9-disease-phenotype-clarification-and-genotype-phenotype-correlation
#6
Michael Alber, Vera M Kalscheuer, Elysa Marco, Elliott Sherr, Gaetan Lesca, Marianne Till, Gyri Gradek, Antje Wiesener, Christoph Korenke, Sandra Mercier, Felicitas Becker, Toshiyuki Yamamoto, Stephen W Scherer, Christian R Marshall, Susan Walker, Usha R Dutta, Ashwin B Dalal, Vanessa Suckow, Payman Jamali, Kimia Kahrizi, Hossein Najmabadi, Berge A Minassian
OBJECTIVE: We aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations. METHODS: Patients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features. RESULTS: A total of 18 patients (including 5 females) were identified...
June 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28571558/protein-profile-analysis-of-two-australian-snake-venoms-by-one-dimensional-gel-electrophoresis-and-ms-ms-experiments
#7
Dessi Georgieva, Diana Hildebrand, Rodrigo Simas, Monika A Coronado, Marcel Kwiatkowski, Hartmut Schlüter, Raghuvir Arni, Patrick Spencer, Christian Betzel
The Pseudechis colletti and Pseudechis butleri venoms were analyzed by 1-D gel electrophoresis, followed by mass spectrometric analysis of tryptic peptides obtained from the protein bands. Both venoms contain highly potent pharmacologically active components, which were assigned to the following protein families: basic and acidic phospholipases A2 (PLA2s), L-amino acid oxidases (LAAOs), P-III metalloproteinases (P-III SVMPs), 5'-nucleotidases (5'-NTDs), cysteine-rich secretory proteins (CRISPs), venom nerve growth factors (VNGFs) and post-synaptic neurotoxins...
May 31, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28569348/black-tar-heroin-skin-popping-as-a-cause-of-wound-botulism
#8
Ihtesham A Qureshi, Mohtashim A Qureshi, Mohammad Rauf Afzal, Alberto Maud, Gustavo J Rodriguez, Salvador Cruz-Flores, Darine Kassar
BACKGROUND: Botulism is a rare potentially fatal and treatable disorder caused by a bacteria-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction. It is caused by either the ingestion of the toxin or the bacteria, inhalation, or wound infection. We present our observations with a descriptive case series of wound botulism secondary to black tar heroin (BTH) injection. METHODS: We report a retrospective single-center case series of 15 consecutive cases of wound botulism presenting to University Medical Center of El Paso...
May 31, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28550022/longitudinal-assessment-of-brain-derived-neurotrophic-factor-in-sardinian-psychotic-patients-labsp-a-protocol-for-a-prospective-observational-study
#9
Diego Primavera, Mirko Manchia, Luca Deriu, Massimo Tusconi, Roberto Collu, Maria Scherma, Paola Fadda, Walter Fratta, Bernardo Carpiniello
INTRODUCTION: Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis...
May 25, 2017: BMJ Open
https://www.readbyqxmd.com/read/28494803/alzheimer-s-disease-dementia-and-stem-cell-therapy
#10
REVIEW
Thomas Duncan, Michael Valenzuela
Alzheimer's disease (AD) represents arguably the most significant social, economic, and medical crisis of our time. Characterized by progressive neurodegenerative pathology, AD is first and foremost a condition of neuronal and synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by exogenous stem cells is therefore a rational therapeutic strategy. This review will focus on recent advances in stem cell therapies utilizing animal models of AD, as well as detailing the human clinical trials of stem cell therapies for AD that are currently undergoing development...
May 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28458021/cerebrolysin-alleviates-cognitive-deficits-induced-by-chronic-cerebral-hypoperfusion-by-increasing-the-levels-of-plasticity-related-proteins-and-decreasing-the-levels-of-apoptosis-related-proteins-in-the-rat-hippocampus
#11
Zhijuan Liu, Ming Hu, Peiyuan Lu, Hebo Wang, Qianqian Qi, Jing Xu, Yining Xiao, Mingyue Fan, Yanqiu Jia, Dandan Zhang
The incidence of vascular dementia (VaD) has rapidly increased over the past few decades. Although officially approved medications for VaD remain limited, cerebrolysin (CBL) had preventive and treatment effects on VaD in some clinical trials. However, the underlying mechanisms have not been determined. The aim of this study was to determine whether CBL protects against cognitive deficits in a rat model of VaD induced by chronic cerebral hypoperfusion by increasing the levels of plasticity-related proteins and decreasing the levels of apoptosis-related proteins...
April 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28438600/neurotrophin-receptors-in-the-pathogenesis-diagnosis-and-therapy-of-neurodegenerative-diseases
#12
REVIEW
Jacopo Meldolesi
In the last few years, exciting properties have emerged regarding the activation, signaling, mechanisms of action, and therapeutic targeting of the two types of neurotrophin receptors: the p75(NTR) with its intracellular and extracellular peptides, the Trks, their precursors and their complexes. This review summarizes these new developments, with particular focus on neurodegenerative diseases. Based on the evolving knowledge, innovative concepts have been formulated regarding the pathogenesis of these diseases, especially the Alzheimer's and two other, the Parkinson's and Huntington's diseases...
April 21, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28362388/analyzing-dendritic-morphology-in-columns-and-layers
#13
Chun-Yuan Ting, Philip G McQueen, Nishith Pandya, Evan S McCreedy, Matthew McAuliffe, Chi-Hon Lee
In many regions of the central nervous systems, such as the fly optic lobes and the vertebrate cortex, synaptic circuits are organized in layers and columns to facilitate brain wiring during development and information processing in developed animals. Postsynaptic neurons elaborate dendrites in type-specific patterns in specific layers to synapse with appropriate presynaptic terminals. The fly medulla neuropil is composed of 10 layers and about 750 columns; each column is innervated by dendrites of over 38 types of medulla neurons, which match with the axonal terminals of some 7 types of afferents in a type-specific fashion...
March 23, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28314733/genetics-implicate-common-mechanisms-in-autism-and-schizophrenia-synaptic-activity-and-immunity
#14
REVIEW
Xiaoming Liu, Zhengwei Li, Conghai Fan, Dongli Zhang, Jiao Chen
The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk...
March 17, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28264432/electrophysiological-characterization-of-the-antarease-metalloprotease-from-tityus-serrulatus-venom
#15
Irene Zornetta, Michele Scorzeto, Pablo Victor Mendes Dos Reis, Maria E De Lima, Cesare Montecucco, Aram Megighian, Ornella Rossetto
Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction...
February 27, 2017: Toxins
https://www.readbyqxmd.com/read/28258674/ibudilast-a-non%C3%A2-selective-phosphodiesterase-inhibitor-in-brain-disorders
#16
Joanna Schwenkgrub, Małgorzata Zaremba, Dagmara Mirowska-Guzel, Iwona Kurkowska-Jastrzębska
Ibudilast (IBD) is a non‑selective (3, 4, 10, 11) phosphodiesterase (PDE) inhibitor, used mainly as a bronchodilator for the treatment of bronchial asthma. PDE play a central role in cellular function (e.g. differentiation, synaptic plasticity and inflammatory response) by metabolizing cyclic nucleotides. The results from preclinical and clinical studies indicate that IBD has a broader range of action through suppression of pro‑inflammatory cytokines (IL‑6, IL‑1β, TNF‑α), toll‑like receptor 4 blockade (TLR‑4), inhibition of a macrophage migration inhibitory factor (MIF), up‑regulation the anti‑inflammatory cytokine (IL‑10), and promotion of neurotrophic factors (GDNF, NGF, NT‑4)...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28251660/neuronal-and-microglial-mechanisms-for-neuropathic-pain-in-the-spinal-dorsal-horn-and-anterior-cingulate-cortex
#17
REVIEW
Makoto Tsuda, Kohei Koga, Tao Chen, Min Zhuo
Neuropathic pain is a debilitating chronic pain condition occurring after damage in the nervous system and is refractory to the currently available treatments. Major challenges include elucidating its mechanisms and developing new medications to treat it. Nerve injury-induced pain hypersensitivity involves aberrant excitability in spinal dorsal horn (SDH) neurons as a consequence of dysfunction of inhibitory interneurons and of hyperactivity of glial cells, especially microglia, the immune cells of the central nervous system...
May 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28241065/repeated-dexamphetamine-treatment-alters-the-dopaminergic-system-and-increases-the-phmri-response-to-methylphenidate
#18
Anouk Schrantee, Jordi L Tremoleda, Marzena Wylezinska-Arridge, Valentine Bouet, Peter Hesseling, Gideon F Meerhoff, Kora M de Bruin, Jan Koeleman, Thomas Freret, Michel Boulouard, Emilie Desfosses, Laurent Galineau, Alessandro Gozzi, François Dauphin, Willy Gsell, Jan Booij, Paul J Lucassen, Liesbeth Reneman
Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28092666/loss-of-%C3%AE-opioid-receptor-signaling-in-nociceptors-but-not-microglia-abrogates-morphine-tolerance-without-disrupting-analgesia
#19
Gregory Corder, Vivianne L Tawfik, Dong Wang, Elizabeth I Sypek, Sarah A Low, Jasmine R Dickinson, Chaudy Sotoudeh, J David Clark, Ben A Barres, Christopher J Bohlen, Grégory Scherrer
Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/27959333/a-single-high-dose-of-dexamethasone-affects-the-phosphorylation-state-of-glutamate-ampa-receptors-in-the-human-limbic-system
#20
M W Lopes, R B Leal, R Guarnieri, M L Schwarzbold, A Hoeller, A P Diaz, G L Boos, K Lin, M N Linhares, J C Nunes, J Quevedo, Z A Bortolotto, H J Markowitsch, S L Lightman, R Walz
Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events...
December 13, 2016: Translational Psychiatry
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