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https://www.readbyqxmd.com/read/28807491/adenosine-a2a-receptor-signaling-affects-il-21-il-22-cytokines-and-gata3-t-bet-transcription-factor-expression-in-cd4-t-cells-from-a-btbr-t-itpr3tf-j-mouse-model-of-autism
#1
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Mashal M Almutairi, Sabry M Attia
Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T(+) Itpr3tf/J (BTBR) mice are used as a model for autism, as they exhibit social deficits, communication deficits, and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral, inflammatory, immune, and neurological disorders...
August 9, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28801311/ethical-issues-when-modelling-brain-disorders-in-non-human-primates
#2
Carolyn P Neuhaus
Non-human animal models of human diseases advance our knowledge of the genetic underpinnings of disease and lead to the development of novel therapies for humans. While mice are the most common model organisms, their usefulness is limited. Larger animals may provide more accurate and valuable disease models, but it has, until recently, been challenging to create large animal disease models. Genome editors, such as Clustered Randomised Interspersed Palindromic Repeat (CRISPR), meet some of these challenges and bring routine genome engineering of larger animals and non-human primates (NHPs) well within reach...
August 11, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28800207/optically-derived-metabolic-and-hemodynamic-parameters-predict-hippocampal-neurogenesis-in-the-btbr-mouse-model-of-autism
#3
David Abookasis, Danit Lerman, Hava Roth, Mati Tfilin, Gadi Turgeman
In the present study, we made use of dual-wavelength laser speckle imaging (DW-LSI) to assess cerebral blood flow in the BTBR genetic mouse model of Autism Spectrum Disorder, as well as control (C57Bl/6J) mice. Since the deficits in social behavior demonstrated by BTBR mice are attributed to changes in neural tissue structure and function, we postulated that these changes can be detected optically using DW-LSI. BTBR mice demonstrated reductions in both cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2 ), as suggested by studies using conventional neuroimaging technologies to reflect impaired neuronal activation and cognitive function...
August 11, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28798977/risperidone-and-aripiprazole-alleviate-prenatal-valproic-acid-induced-abnormalities-in-behaviors-and-dendritic-spine-density-in-mice
#4
Yuta Hara, Yukio Ago, Atsuki Taruta, Shigeru Hasebe, Haruki Kawase, Wataru Tanabe, Shinji Tsukada, Takanobu Nakazawa, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
RATIONALE: Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities. We recently found that prenatal VPA exposure causes hypofunction of the prefrontal dopaminergic system in mice. This suggests that the dopaminergic system may be a potential pharmacological target for treatment of behavioral abnormalities in ASD patients. OBJECTIVES: In the present study, we examined the effects of antipsychotic drugs, which affect the dopaminergic system, on the social interaction deficits, recognition memory impairment, and reduction in dendritic spine density in the VPA mouse model of ASD...
August 10, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28796901/from-peroxisomal-disorders-to-common-neurodegenerative-diseases-the-role-of-ether-phospholipids-in-the-nervous-system
#5
REVIEW
Fabian Dorninger, Sonja Forss-Petter, Johannes Berger
The emerging diverse roles of ether (phospho)lipids in nervous system development and function in health and disease are currently attracting growing interest. Plasmalogens, a subgroup of ether lipids, are important membrane components involved in vesicle fusion and membrane raft composition. They store polyunsaturated fatty acids and may serve as antioxidants. Ether lipid metabolites act as precursors for the formation of glycosyl-phosphatidyl-inositol (GPI) anchors; others, like platelet-activating factor, are implicated in signaling functions...
August 10, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28795135/male-and-female-mice-lacking-neuroligin-3-modify-the-behavior-of-their-wild-type-littermates
#6
Shireene Kalbassi, Sven O Bachmann, Ellen Cross, Victoria H Roberton, Stéphane J Baudouin
In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other's behavior. We have found that, when raised together, male Nlgn3 knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male Nlgn3 knockout mice correlated with an increase in their anxiety...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28776581/decreased-brain-ph-as-a-shared-endophenotype-of-psychiatric-disorders
#7
Hideo Hagihara, Vibeke S Catts, Yuta Katayama, Hirotaka Shoji, Tsuyoshi Takagi, Freesia L Huang, Akito Nakao, Yasuo Mori, Kuo-Ping Huang, Shunsuke Ishii, Isabella A Graef, Keiichi I Nakayama, Cynthia Shannon Weickert, Tsuyoshi Miyakawa
Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models, which can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing datasets from ten studies...
August 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28774750/advances-in-nonhuman-primate-models-of-autism-integrating-neuroscience-and-behavior
#8
REVIEW
M D Bauman, C S Schumann
Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research are needed to (i) identify and evaluate putative causes of ASD, (ii) determine the underlying neurobiological mechanisms, (iii) develop and test novel therapeutic approaches and (iv) ultimately translate basic research into safe and effective clinical practices...
July 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28768803/modulation-of-prefrontal-cortex-excitation-inhibition-balance-rescues-social-behavior-in-cntnap2-deficient-mice
#9
Aslihan Selimbeyoglu, Christina K Kim, Masatoshi Inoue, Soo Yeun Lee, Alice S O Hong, Isaac Kauvar, Charu Ramakrishnan, Lief E Fenno, Thomas J Davidson, Matthew Wright, Karl Deisseroth
Alterations in the balance between neuronal excitation and inhibition (E:I balance) have been implicated in the neural circuit activity-based processes that contribute to autism phenotypes. We investigated whether acutely reducing E:I balance in mouse brain could correct deficits in social behavior. We used mice lacking the CNTNAP2 gene, which has been implicated in autism, and achieved a temporally precise reduction in E:I balance in the medial prefrontal cortex (mPFC) either by optogenetically increasing the excitability of inhibitory parvalbumin (PV) neurons or decreasing the excitability of excitatory pyramidal neurons...
August 2, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28764956/microbiome-and-metabolome-data-integration-provides-insight-into-health-and-disease
#10
REVIEW
Michael Shaffer, Abigail J S Armstrong, Vanessa V Phelan, Nichole Reisdorph, Catherine A Lozupone
For much of our history, the most basic information about the microbial world has evaded characterization. Next-generation sequencing has led to a rapid increase in understanding of the structure and function of host-associated microbial communities in diverse diseases ranging from obesity to autism. Through experimental systems such as gnotobiotic mice only colonized with known microbes, a causal relationship between microbial communities and disease phenotypes has been supported. Now, microbiome research must move beyond correlations and general demonstration of causality to develop mechanistic understandings of microbial influence, including through their metabolic activities...
July 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28753255/comprehensive-analysis-of-two-shank3-and-the-cacna1c-mouse-models-of-autism-spectrum-disorder
#11
Patricia Kabitzke, Daniela Brunner, Dansha He, Pamela A Fazio, Kimberly Cox, Jane Sutphen, Lucinda Thiede, Emily Sabath, Taleen Hanania, Vadim Alexandrov, Randall Rasmusson, Will Spooren, Anirvan Ghosh, Pamela Feliciano, Barbara Biemans, Marta Benedetti, Alice Luo Clayton
To expand, analyze, and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng's Shank3(tm2Gfng) model, hereafter Shank3/F, Jiang's Shank3(tm1Yhj) model, hereafter Shank3/J, and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. The current study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11...
July 28, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28743991/altered-visual-cortical-processing-in-a-mouse-model-of-mecp2-duplication-syndrome
#12
Dinghong Zhang, Bin Yu, Jing Liu, Weiqian Jiang, Taorong Xie, Ran Zhang, Dali Tong, Zilong Qiu, Haishan Yao
As an epigenetic modulator of gene expression, Methyl-CpG binding protein 2 (MeCP2) is essential for normal neurological function. Dysfunction of MeCP2 is associated with a variety of neurological disorders. MECP2 gene duplication in human causes neuropsychiatric symptoms such as mental retardation and autism. MeCP2 overexpression in mice results in neurobehavioural disorders, dendritic abnormalities, and synaptic defects. However, how gain of MeCP2 function influences cortical processing of sensory information remains unclear...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743598/decrease-in-endogenous-brain-allopregnanolone-induces-autism-spectrum-disorder-asd-like-behavior-in-mice-a-novel-animal-model-of-asd
#13
Ken Ebihara, Hironori Fujiwara, Suresh Awale, Dya Fita Dibwe, Ryota Araki, Takeshi Yabe, Kinzo Matsumoto
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms of social impairments and restrictive repetitive behaviors. Recent evidence has implicated a dysfunction in the GABAergic system in the pathophysiology of ASD. We investigated the role of endogenous allopregnanolone (ALLO), a neurosteroidal positive allosteric modulator of GABAA receptors, in the regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor of type I and type II 5α-reductase, a rate-limiting enzyme of ALLO biosynthesis...
July 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28740469/neuroligins-nlg2-and-nlg4-affect-social-behavior-in-drosophila-melanogaster
#14
Kristina Corthals, Alina Sophia Heukamp, Robert Kossen, Isabel Großhennig, Nina Hahn, Heribert Gras, Martin C Göpfert, Ralf Heinrich, Bart R H Geurten
The genome of Drosophila melanogaster includes homologs to approximately one-third of the currently known human disease genes. Flies and humans share many biological processes, including the principles of information processing by excitable neurons, synaptic transmission, and the chemical signals involved in intercellular communication. Studies on the molecular and behavioral impact of genetic risk factors of human neuro-developmental disorders [autism spectrum disorders (ASDs), schizophrenia, attention deficit hyperactivity disorders, and Tourette syndrome] increasingly use the well-studied social behavior of D...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28736241/oxytocin-release-via-activation-of-trpm2-and-cd38-in-the-hypothalamus-during-hyperthermia-in-mice-implication-for-autism-spectrum-disorder
#15
REVIEW
Haruhiro Higashida, Teruko Yuhi, Shirin Akther, Sarwat Amina, Jing Zhong, Mingkun Liang, Tomoko Nishimura, Hong-Xiang Liu, Olga Lopatina
Oxytocin (OT) is a critical molecule for social recognition that mediates social and emotional behaviors. OT is released during stress and acts as an anxiolytic factor. To know the precise molecular mechanisms underlying OT release into the brain during stress is important. It has been reported that intracellular concentrations of free calcium in the hypothalamic neurons are elevated by simultaneous stimulation of cyclic ADP-ribose (cADPR) and heat. We have reported in vitro and in vivo data that supports the idea that release of OT in the brain of male mice is regulated by cADPR and fever in relation to stress conditions...
July 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28724750/disruption-of-a-structurally-important-extracellular-element-in-the-glycine-receptor-leads-to-decreased-synaptic-integration-and-signaling-resulting-in-severe-startle-disease
#16
Natascha Schaefer, Alexandra Berger, Johannes van Brederode, Fang Zheng, Yan Zhang, Sophie Leacock, Laura Littau, Sibylle Jablonka, Sony Malhotra, Maya Topf, Friederike Winter, Daria Davydova, Joseph W Lynch, Christopher J Paige, Christian Alzheimer, Robert J Harvey, Carmen Villmann
Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorder. We found that lack of synaptic integration of GlyRs, together with disrupted receptor function is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation Q177K located in the extracellular β8-β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8-β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in cys-loop receptors...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28723388/region-specific-impairments-in-parvalbumin-interneurons-in-social-isolation-reared-mice
#17
Hiroshi Ueno, Shunsuke Suemitsu, Shinji Murakami, Naoya Kitamura, Kenta Wani, Motoi Okamoto, Yosuke Matsumoto, Takeshi Ishihara
Many neuropsychiatric disorders show localized dysfunction in specific cortical regions. The mechanisms underlying such region-specific vulnerabilities are unknown. Post-mortem analyses have demonstrated a selective reduction in the expression of parvalbumin (PV) in GABAergic interneurons in the frontal rather than the sensory cortex of patients with neuropsychiatric disorders such as schizophrenia, autism spectrum disorders, and bipolar disorders. PV neurons are surrounded by perineuronal nets (PNNs), and are protected from oxidative stress...
July 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28720486/loss-of-synaptic-zinc-transport-in-progranulin-deficient-mice-may-contribute-to-progranulin-associated-psychopathology-and-chronic-pain
#18
Stefanie Hardt, Juliana Heidler, Boris Albuquerque, Lucie Valek, Christine Altmann, Annett Wilken-Schmitz, Michael K E Schäfer, Ilka Wittig, Irmgard Tegeder
Affective and cognitive processing of nociception contributes to the development of chronic pain and vice versa, pain may precipitate psychopathologic symptoms. We hypothesized a higher risk for the latter with immanent neurologic diseases and studied this potential interrelationship in progranulin-deficient mice, which are a model for frontotemporal dementia, a disease dominated by behavioral abnormalities in humans. Young naïve progranulin deficient mice behaved normal in tests of short-term memory, anxiety, depression and nociception, but after peripheral nerve injury, they showed attention-deficit and depression-like behavior, over-activity, loss of shelter-seeking, reduced impulse control and compulsive feeding behavior, which did not occur in equally injured controls...
July 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28719137/neocortical-developmental-analysis-of-vasculature-and-their-growth-factors-offer-new-insight-into-fragile-x-syndrome-abnormalities
#19
Amogh P Belagodu, Stephen Fleming, Roberto Galvez
Fragile X Syndrome (FXS) is the most common single gene cause for Autism Spectrum Disorder and the most prevalent form of inherited mental retardation. Our prior studies have demonstrated that adult FXS mice have abnormal blood vessel density (BVD) and elevated Vascular Endothelial Growth Factor A expression (VEGF-A). VEGF-A is one of the most prominent regulators of BVD, and its abnormal expression is the most likely cause for FXS BVD abnormalities. We have demonstrated that attenuating elevated VEGF-A expression can ameliorate many non-vascular FXS abnormalities (Belagodu, Zendeli Slater and Galvez: Dev Neurobiol 77 (2017) 14-25), suggesting that abnormal VEGF-A expression is an underlying cause for some FXS abnormalities...
July 18, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28713243/synaptic-interactome-mining-reveals-p140cap-as-a-new-hub-for-psd-proteins-involved-in-psychiatric-and-neurological-disorders
#20
Annalisa Alfieri, Oksana Sorokina, Annie Adrait, Costanza Angelini, Isabella Russo, Alessandro Morellato, Michela Matteoli, Elisabetta Menna, Elisabetta Boeri Erba, Colin McLean, J Douglas Armstrong, Ugo Ala, Joseph D Buxbaum, Alfredo Brusco, Yohann Couté, Silvia De Rubeis, Emilia Turco, Paola Defilippi
Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines...
2017: Frontiers in Molecular Neuroscience
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