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autism mice

Owen Y Chao, Richelle Yunger, Yi-Mei Yang
Autism spectrum disorders (ASD) are diagnosed based on the behavioral criteria of impaired social interaction, defective communication and repetitive behaviors. Psychiatric comorbidities, such as anxiety and intellectual disability, are commonly present in ASD. The BTBR T+Itpr3tf/J (BTBR) mice display a range of autistic phenotypes, yet whether this mouse model is appropriate to study psychiatric comorbidity in ASD remains unclear. We addressed this issue by subjecting the BTBR animals to three-chambered apparatus, open field, object attention test and elevated open platform...
March 12, 2018: Behavioural Brain Research
Changqing Lu, Lihua Dong, Hui Zhou, Qianmei Li, Guojiao Huang, Shu Jun Bai, Linchuan Liao
Oligodendrocytes are the myelin-producing cells of the central nervous system (CNS). A variety of brain disorders from "classical" demyelinating diseases, such as multiple sclerosis, stroke, schizophrenia, depression, Down syndrome and autism, are shown myelination defects. Oligodendrocyte myelination is regulated by a complex interplay of intrinsic, epigenetic and extrinsic factors. Gpr17 (G protein-coupled receptor 17) is a G protein-coupled receptor, and has been identified to be a regulator for oligodendrocyte development...
March 14, 2018: Scientific Reports
Jacque P K Ip, Ikue Nagakura, Jeremy Petravicz, Keji Li, Erik A C Wiemer, Mriganka Sur
Microdeletion of a region in chromosome 16p11.2 increases susceptibility to autism. Although this region contains exons of 29 genes, disrupting only a small segment of the region, which spans 5 genes, is sufficient to cause autistic traits. One candidate gene in this critical segment is MVP , which encodes for the major vault protein (MVP) that has been implicated in regulation of cellular transport mechanisms. MVP expression levels in MVP +/- mice closely phenocopy those of 16p11.2 mutant mice, suggesting that MVP +/- mice may serve as a model of MVP function in 16p11...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Luye Qin, Kaijie Ma, Zi-Jun Wang, Zihua Hu, Emmanuel Matas, Jing Wei, Zhen Yan
Haploinsufficiency of the SHANK3 gene is causally linked to autism spectrum disorder (ASD), and ASD-associated genes are also enriched for chromatin remodelers. Here we found that brief treatment with romidepsin, a highly potent class I histone deacetylase (HDAC) inhibitor, alleviated social deficits in Shank3-deficient mice, which persisted for ~3 weeks. HDAC2 transcription was upregulated in these mice, and knockdown of HDAC2 in prefrontal cortex also rescued their social deficits. Nuclear localization of β-catenin, a Shank3-binding protein that regulates cell adhesion and transcription, was increased in Shank3-deficient mice, which induced HDAC2 upregulation and social deficits...
March 12, 2018: Nature Neuroscience
Adeline A Lau, Sarah J Tamang, Kim M Hemsley
Mucopolysaccharidosis (MPS) type IIIA is an inherited, neurodegenerative lysosomal storage disorder resulting from mutations in the SGSH gene. Consequently, N-sulphoglucosamine sulphohydrolase enzyme activity is reduced resulting in impaired catabolism of heparan sulphate. After an asymptomatic period, patients typically show a progressive loss of cognitive and motor skills, with death often during the second decade of life. The diagnostic criteria of autism spectrum disorders (ASD) include impaired communication and social interactions, as well as displays of repetitive behaviours and fixed interests...
March 8, 2018: Journal of Inherited Metabolic Disease
A Özge Sungur, Lea Stemmler, Markus Wöhr, Marco B Rust
Autism spectrum disorder (ASD), schizophrenia (SCZ) and intellectual disability (ID) show a remarkable overlap in symptoms, including impairments in cognition, social behavior and communication. Human genetic studies revealed an enrichment of mutations in actin-related genes for these disorders, and some of the strongest candidate genes control actin dynamics. These findings led to the hypotheses: (i) that ASD, SCZ and ID share common disease mechanisms; and (ii) that, at least in a subgroup of affected individuals, defects in the actin cytoskeleton cause or contribute to their pathologies...
2018: Frontiers in Behavioral Neuroscience
Julie Sadino, Zoe Donaldson
Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related, but non-monogamous meadow and montane voles, have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species...
March 7, 2018: ACS Chemical Neuroscience
Dake Song, Yaping Ge, Zhaodi Chen, Chao Shang, Ying Guo, Taiyun Zhao, Yunfeng Li, Ning Wu, Rui Song, Jin Li
Post-traumatic stress disorder (PTSD) is a complicated psychiatric disorder, which occurs after exposure to a traumatic event. The main clinical manifestation of PTSD includes fear and stress dysregulation. In both animals and humans, dysregulation of dopamine function appears to be related to conditioned fear responses. Previous studies show that the dopamine D3 receptor (D3R) is involved in schizophrenia, autism, and substance use disorders and is related to emotional disorders. However, few studies have investigated the role of the D3R in the pathogenesis and aetiology of PTSD...
March 3, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Federica Filice, Emanuel Lauber, Karl Jakob Vörckel, Markus Wöhr, Beat Schwaller
Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by two core symptoms: impaired social interaction and communication, and restricted, repetitive behaviors and interests. The pathophysiology of ASD is not yet fully understood, due to a plethora of genetic and environmental risk factors that might be associated with or causal for ASD. Recent findings suggest that one putative convergent pathway for some forms of ASD might be the downregulation of the calcium-binding protein parvalbumin (PV)...
2018: Molecular Autism
Yulong Cai, Xiaotong Tang, Xi Chen, Xin Li, Ying Wang, Xiaohang Bao, Lian Wang, Dayu Sun, Jinghui Zhao, Yan Xing, Margaret Warner, Haiwei Xu, Jan-Åke Gustafsson, Xiaotang Fan
The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor β (LXRβ) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Wei Cao, Shen Lin, Qiang-Qiang Xia, Yong-Lan Du, Qian Yang, Meng-Ying Zhang, Yi-Qing Lu, Jing Xu, Shu-Min Duan, Xia Jun, Guoping Feng, Junyu Xu, Jian-Hong Luo
Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice...
February 22, 2018: Neuron
Yan Li, Galen Missig, Beate C Finger, Samantha M Landino, Abigail J Alexander, Emery Mokler, James Robbins, Yunona Manasian, Woori Kim, Kwang-Soo Kim, Christopher J McDougle, William A Carlezon, Vadim Y Bolshakov
Inflammatory processes may be involved in the pathophysiology of neuropsychiatric illnesses including Autism Spectrum Disorder (ASD). Evidence from studies in rodents indicates that immune activation during early development can produce core features of ASD (social interaction deficits, dysregulation of communication, increases in stereotyped behaviors and anxiety), although the neural mechanisms of these effects are not thoroughly understood. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, or vehicle on gestational day 12...
February 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tara Arbab, Francesco P Battaglia, Cyriel M A Pennartz, Conrado A Bosman
Neuronal networks can synchronize their activity through excitatory and inhibitory connections, which is conducive to synaptic plasticity. This synchronization is reflected in rhythmic fluctuations of the extracellular field. In the hippocampus, theta and gamma band LFP oscillations are a hallmark of the processing of spatial information and memory. Fragile X syndrome (FXS) is an intellectual disability and the most common genetic cause of autism spectrum disorder (Belmonte and Bourgeron, 2006). Here, we investigated how neuronal network synchronization in the mouse hippocampus is compromised by the Fmr1 mutation that causes FXS (Santos et al...
February 24, 2018: Neurobiology of Disease
Fu-Sun Lo, Reha S Erzurumlu
Background: Met receptor tyrosine kinase regulates neurogenesis, differentiation, migration, connectivity, and synaptic plasticity. The human Met gene has been identified as a prominent risk factor for autism spectrum disorder (ASD). Met gene-altered mice serve as useful models for mechanistic studies of ASD. Inactivation of Met in excitatory cortical neurons in mice ( Emx1 cre /Met flox mice) yields a phenotype in which significantly decreased GABAA receptor-mediated inhibition shifts the excitation/inhibition (E/I) balance toward excitation in the somatosensory cortex...
2018: Molecular Autism
Zahra Namvarpour, Mohammad Nasehi, Abdollah Amini, Mohammad-Reza Zarrindast
Aim Thimerosal, a mercury-containing preservative has been widely used in a number of biological and drug products, including many vaccines, and has been studied as a possible etiological factor for some neurodevelopmental disabilities. Here, the protective effects of Alpha Lipoic Acid (ALA), an organosulfur compound derived from Octanoic Acid, on Thimerosal-induced behavioral abnormalities in rat were examined. METHODS: 108 male Wistar rats were divided into three cohorts and treated as follows: 1) Thimerosal at different doses (30, 300, or 3000 μg Hg/kg) in four i...
February 23, 2018: Neurotoxicology and Teratology
Young-A Lee, Tsukasa Obora, Laura Bondonny, Amelie Toniolo, Johanna Mivielle, Yoshie Yamaguchi, Akemi Kato, Masatoshi Takita, Yukiori Goto
Population density has been suggested to affect social interactions of individuals, but the underlying neural mechanisms remain unclear. In contrast, neurotransmission of monoamines such as serotonin (5-HT) and dopamine (DA) has been demonstrated to play important roles in social behaviors. Here, we investigated whether housing density affected social interactions of rodents and non-human primates housed in groups, and its correlations with monoamines. Japanese macaques exhibited higher plasma 5-HT, but not DA, concentrations than rhesus macaques...
February 22, 2018: Scientific Reports
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Mohammad Z Alzahrani, Saleh A Bakheet, Sabry M Attia
Autism is a neurodevelopmental disorder characterized by deficits in qualitative impairments in communication, repetitive and social interaction, restricted, and stereotyped patterns of behavior. Resveratrol has been extensively studied pharmacologically and biologically and has anti-inflammatory, antioxidant, and neuroprotective effects on neuronal damage in neurodegenerative disorders. The BTBR T+ Itpr3tf /J (BTBR) autistic mouse model has been explored for treatment of autism, which shows low reciprocal social interactions, impaired juvenile play, and decreased social approach...
February 21, 2018: Neuromolecular Medicine
Melanie Richter, Nadeem Murtaza, Robin Scharrenberg, Sean H White, Ole Johanns, Susan Walker, Ryan K C Yuen, Birgit Schwanke, Bianca Bedürftig, Melad Henis, Sarah Scharf, Vanessa Kraus, Ronja Dörk, Jakob Hellmann, Zsuzsa Lindenmaier, Jacob Ellegood, Henrike Hartung, Vickie Kwan, Jan Sedlacik, Jens Fiehler, Michaela Schweizer, Jason P Lerch, Ileana L Hanganu-Opatz, Fabio Morellini, Stephen W Scherer, Karun K Singh, Froylan Calderon de Anda
Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission...
February 21, 2018: Molecular Psychiatry
Livia H Morais, Daniela Felice, Anna V Golubeva, Gerard Moloney, Timothy G Dinan, John F Cryan
There is a growing realization that the severity of the core symptoms of autism spectrum disorders and schizophrenia is associated with gastrointestinal dysfunction. Nonetheless, the mechanisms underlying such comorbidities remain unknown. Several genetic and environmental factors have been linked to a higher susceptibility to neurodevelopmental abnormalities. The maternal immune activation (MIA) rodent model is a valuable tool for elucidating the basis of this interaction. We induced MIA with polyinosinic-polycytidylic acid (poly I:C) at gestational day 12...
February 16, 2018: Behavioural Pharmacology
Brian C Shonesy, Walker P Parrish, Hala K Haddad, Jason R Stephenson, Rita Báldi, Rebecca J Bluett, Christian R Marks, Samuel W Centanni, Oakleigh M Folkes, Keeley Spiess, Shana M Augustin, Ken Mackie, David M Lovinger, Danny G Winder, Sachin Patel, Roger J Colbran
BACKGROUND: Endocannabinoid signaling plays an important role in regulating synaptic transmission in the striatum, a brain region implicated as a central node of dysfunction in autism spectrum disorder. Deficits in signaling mediated by the endocannabinoid 2-arachidonoylglycerol (2-AG) have been reported in mouse models of autism spectrum disorder, but a causal role for striatal 2-AG deficiency in phenotypes relevant to autism spectrum disorder has not been explored. METHODS: Using conditional knockout mice, we examined the electrophysiological, biochemical, and behavioral effects of 2-AG deficiency by deleting its primary synthetic enzyme, diacylglycerol lipase α (DGLα), from dopamine D1 receptor-expressing or adenosine A2a receptor-expressing medium spiny neurons (MSNs) to determine the role of 2-AG signaling in striatal direct or indirect pathways, respectively...
December 28, 2017: Biological Psychiatry
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