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https://read.qxmd.com/read/30885608/rescue-by-4-phenylbutyrate-of-several-misfolded-creatine-transporter-1-variants-linked-to-the-creatine-transporter-deficiency-syndrome
#1
REVIEW
Ali El-Kasaby, Ameya Kasture, Florian Koban, Matej Hotka, HafizM M Asjad, Helmut Kubista, Michael Freissmuth, Sonja Sucic
Diseases arising from misfolding of SLC6 transporters have been reported over recent years, e.g. folding-deficient mutants of the dopamine transporter and of the glycine transporter-2 cause infantile/juvenile Parkinsonism dystonia and hyperekplexia, respectively. Mutations in the coding sequence of the human creatine transporter-1 (hCRT-1/SLC6A8) gene result in a creatine transporter deficiency syndrome, which varies in its clinical manifestation from epilepsy, mental retardation, autism, development delay and motor dysfunction to gastrointestinal symptoms...
March 15, 2019: Neuropharmacology
https://read.qxmd.com/read/30877790/deletion-of-the-kh1-domain-of-fmr1-leads-to-transcriptional-alterations-and-attentional-deficits-in-rats
#2
Carla E M Golden, Michael S Breen, Lacin Koro, Sankalp Sonar, Kristi Niblo, Andrew Browne, Natalie Burlant, Daniele Di Marino, Silvia De Rubeis, Mark G Baxter, Joseph D Buxbaum, Hala Harony-Nicolas
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene. It is a leading monogenic cause of autism spectrum disorder and inherited intellectual disability and is often comorbid with attention deficits. Most FXS cases are due to an expansion of CGG repeats leading to suppressed expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA metabolism. We found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1...
March 16, 2019: Cerebral Cortex
https://read.qxmd.com/read/30848474/impaired-spatial-cognition-in-adult-rats-treated-with-multiple-intracerebroventricular-icv-infusions-of-the-enteric-bacterial-metabolite-propionic-acid-and-return-to-baseline-after-1-week-of-no-treatment-contribution-to-a-rodent-model-of-asd
#3
Jennifer R Mepham, Francis H Boon, Kelly A Foley, Donald P Cain, Derrick F MacFabe, Klaus-Peter Ossenkopp
Propionic acid (PPA) is a dietary short chain fatty acid and an enteric bacterial metabolite. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioral changes similar to those seen in autism spectrum disorders (ASD), including perseveration. The effects of ICV infusions of PPA on spatial cognition were examined by giving rats infusions of either PPA (0.26 M, pH 7.4, 4 μl/infusion) or phosphate-buffered saline (PBS, 0.1 M) twice a day for 7 days. The rats were then tested in the Morris water maze (MWM) for acquisition of spatial learning...
March 8, 2019: Neurotoxicity Research
https://read.qxmd.com/read/30792426/consequences-of-prenatal-exposure-to-valproic-acid-in-the-socially-monogamous-prairie-voles
#4
L Sailer, F Duclot, Z Wang, M Kabbaj
Environmental risk factors contribute to autism spectrum disorders (ASD) etiology. In particular, prenatal exposure to the highly teratogenic anticonvulsant valproic acid (VPA) significantly increases ASD prevalence. Although significant discoveries on the embryopathology of VPA have been reported, its effects on the ability to form enduring social attachment-characteristic of ASD but uncommonly displayed by rats and mice-remains unknown. We aimed to examine the effects of prenatal VPA exposure in the social, monogamous prairie voles (Microtus ochrogaster)...
February 21, 2019: Scientific Reports
https://read.qxmd.com/read/30790215/neuroligins-differentially-mediate-subtype-specific-synapse-formation-in-pyramidal-neurons-and-interneurons
#5
Qiang-Qiang Xia, Jing Xu, Tai-Lin Liao, Jie Yu, Lei Shi, Jun Xia, Jian-Hong Luo, Junyu Xu
Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons...
February 21, 2019: Neuroscience Bulletin
https://read.qxmd.com/read/30769127/benefits-of-fenofibrate-in-prenatal-valproic-acid-induced-autism-spectrum-disorder-related-phenotype-in-rats
#6
Roohi Mirza, Bhupesh Sharma
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with two major behavioral symptoms i.e. repetitive behavior and social-communication impairment. The unknown etiology of ASD is responsible for the difficulty in identifying the possible therapeutic modulators for ASD. Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy. Therefore, prenatal exposure of VPA induced autism spectrum disorder like phenotypes in both human and rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-α) is widely localized in the brain...
February 12, 2019: Brain Research Bulletin
https://read.qxmd.com/read/30689218/systemic-treatment-with-the-enteric-bacterial-metabolic-product-propionic-acid-results-in-reduction-of-social-behavior-in-juvenile-rats-contribution-to-a-rodent-model-of-autism-spectrum-disorder
#7
Soaleha Shams, Kelly A Foley, Martin Kavaliers, Derrick F MacFabe, Klaus-Peter Ossenkopp
The role of the gut microbiome and its enteric metabolites, such as short-chain fatty acids (SCFAs), in the etiology of autism spectrum disorders (ASDs) has recently received increased attention. Of particular interest has been the SCFA, propionic acid (PPA). Several different rodent models have been developed using PPA treatment to examine behaviors of relevance to ASD. The effects of systemic (intraperitoneal, i.p.) administration of PPA on social behavior, anxiety-related behavior, and locomotor activity in juvenile male rats (age 35 days) were examined in this study...
January 28, 2019: Developmental Psychobiology
https://read.qxmd.com/read/30682436/abnormal-empathy-like-pro-social-behaviour-in-the-valproic-acid-model-of-autism-spectrum-disorder
#8
Mellanie Fontes-Dutra, Gustavo Della-Flora Nunes, Julio Santos Terra, Walquíria Souza-Nunes, Guilherme Bauer-Negrini, Mauro Mozael Hirsch, Lily Green, Rudimar Riesgo, Carmem Gottfried, Victorio Bambini-Junior
Impairments in social behaviour are a defining feature of autism spectrum disorder (ASD). Individuals with ASD also usually present some difficulty to recognise or understand another person's feelings. Therefore, it is possible that altered empathy processing could hinder typical social interaction in ASD. Recently, robust paradigms confirmed that rodents show primordial forms of empathy-like behaviour. Therefore, in this work, we used one of these new protocols to test pro-social behaviour in the rat model of autism induced by Valproic Acid (VPA)...
January 22, 2019: Behavioural Brain Research
https://read.qxmd.com/read/30643788/regulation-of-the-expression-of-the-psychiatric-risk-gene-cacna1c-during-associative-learning
#9
Lucy Sykes, Nicholas E Clifton, Jeremy Hall, Kerrie L Thomas
CACNA1C encodes the Cav 1.2 L-type voltage-gated calcium channel. Generic variation in CACNA1C has been consistently identified as associated with risk for psychiatric disorders including schizophrenia, bipolar disorder, major depressive disorder and autism. Psychiatric risk loci are also enriched for genes involved in the regulation of synaptic plasticity. Here, we show that the expression of Cacna1c is regulated in the rat hippocampus after context exposure, contextual fear conditioning and fear memory retrieval in a manner that correlates to specific memory processes...
December 2018: Molecular Neuropsychiatry
https://read.qxmd.com/read/30582116/microglia-activation-in-the-offspring-of-prenatal-poly-i-c-exposed-rats-a-pet-imaging-and-immunohistochemistry-study
#10
Xue Li, Xin Tian, Luxian Lv, Gangrui Hei, Xufeng Huang, Xiaoduo Fan, Jinming Zhang, Jianjiang Zhang, Lijuan Pang, Xueqin Song
Background: The well-known 'pyrotherapy' of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic-polyribocytidilicacid (Poly I:C) during pregnancy using 11 C-PK11195 positron emission tomography (PET) and immunohistochemistry...
2018: General Psychiatry
https://read.qxmd.com/read/30557783/convergent-microstructural-brain-changes-across-genetic-models-of-autism-spectrum-disorder-a-pilot-study
#11
Paul A Rowley, Jose Guerrero-Gonzalez, Andrew L Alexander, John-Paul J Yu
Autism spectrum disorder (ASD) is a complex and genetically heterogeneous neuropsychiatric disease affecting as many as 1 in 68 children. Large scale genetic sequencing of individuals along the autism spectrum has uncovered several genetic risk factors for ASD; however, understanding how, and to what extent, individual genes contribute to the overall disease phenotype remains unclear. Neuroimaging studies of ASD have revealed a wide spectrum of structural and functional perturbations that are thought to reflect, in part, the complex genetic heterogeneity underpinning ASD...
December 8, 2018: Psychiatry Research. Neuroimaging
https://read.qxmd.com/read/30555669/the-valproic-acid-rat-model-of-autism-presents-with-gut-bacterial-dysbiosis-similar-to-that-in-human-autism
#12
Fang Liu, Kayla Horton-Sparks, Vanessa Hull, Robert W Li, Verónica Martínez-Cerdeño
Background: Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease. Methods: We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism...
2018: Molecular Autism
https://read.qxmd.com/read/30537517/hyperexcitability-of-hippocampal-ca1-pyramidal-neurons-in-male-offspring-of-a-rat-model-of-autism-spectrum-disorder-asd-induced-by-prenatal-exposure-to-valproic-acid-a-possible-involvement-of-ih-channel-current
#13
Razieh Hajisoltani, Seyed Asaad Karimi, Mona Rahdar, Shima Davoudi, Mehdi Borjkhani, Narges Hosseinmardi, Gila Behzadi, Mahyar Janahmadi
Autism spectrum disorder (ASD) is a common neuropsychiatric disorder, which is characterized by impairment in social interaction and cognitive behaviors. However, there is not much electrophysiological data available on alterations of neuronal excitability in autism. Here, we assessed the pattern of neuronal excitability and the possible contribution of Ih current to the altered excitability of hippocampal CA1 pyramidal neurons in a rat model of VPA-induced ASD-like behavior. Pregnant Wistar rats received Valproic Acid (VPA, 500mg/kg) at gestational day 12...
December 8, 2018: Brain Research
https://read.qxmd.com/read/30510526/prenatal-progestin-exposure-is-associated-with-autism-spectrum-disorders
#14
Ling Li, Min Li, Jianping Lu, Xiaohu Ge, Weiguo Xie, Zichen Wang, Xiaoling Li, Chao Li, Xiaoyan Wang, Yan Han, Yifei Wang, Liyan Zhong, Wei Xiang, Xiaodong Huang, Haijia Chen, Paul Yao
We have previously reported that prenatal progestin exposure induces autism-like behavior in offspring through ERβ (estrogen receptor β) suppression in the brain, indicating that progestin may induce autism spectrum disorders (ASD). In this study, we aim to investigate whether prenatal progestin exposure is associated with ASD. A population-based case-control epidemiology study was conducted in Hainan province of China. The ASD children were first screened with the Autism Behavior Checklist (ABC) questionnaire, and then diagnosed by clinical professionals using the ASD diagnosis criteria found in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)...
2018: Frontiers in Psychiatry
https://read.qxmd.com/read/30505268/glutamate-glutamine-and-gaba-levels-in-rat-brain-measured-using-mrs-hplc-and-nmr-methods-in-study-of-two-models-of-autism
#15
Elzbieta Zieminska, Beata Toczylowska, Dominik Diamandakis, Wojciech Hilgier, Robert Kuba Filipkowski, Rafal Polowy, Jaroslaw Orzel, Michal Gorka, Jerzy Wieslaw Lazarewicz
The disorders of the glutamatergic neurotransmission have been associated with pathogenesis of autism. In this study we evaluated the impact of the in vivo and ex vivo test methodology on measurements of levels of neurotransmitter amino acids in hippocampus of rats for valproic acid- (VPA) and thalidomide- (THAL) induced models of autism. The main goal was to compare the changes in concentrations of glutamate (Glu), glutamine (Gln) and GABA between both autistic groups and the control, measured in vivo and ex vivo in homogenates...
2018: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/30459605/potentiation-of-glutamatergic-synaptic-transmission-onto-dorsal-raphe-serotonergic-neurons-in-the-valproic-acid-model-of-autism
#16
Ruixiang Wang, Kathryn Hausknecht, Roh-Yu Shen, Samir Haj-Dahmane
Autism spectrum disorder (ASD) is characterized by social and communicative impairments and increased repetitive behaviors. These symptoms are often comorbid with increased anxiety. Prenatal exposure to valproic acid (VPA), an anti-seizure and mood stabilizer medication, is a major environmental risk factor of ASD. Given the important role of the serotonergic (5-HT) system in anxiety, we examined the impact of prenatal VPA exposure on the function of dorsal raphe nucleus (DRn) 5-HT neurons. We found that male rats prenatally exposed to VPA exhibited increased anxiety-like behaviors revealed by a decreased time spent on the open arms of the elevated plus maze...
2018: Frontiers in Pharmacology
https://read.qxmd.com/read/30429780/behavioral-plasticity-of-audiovisual-perception-rapid-recalibration-of-temporal-sensitivity-but-not-perceptual-binding-following-adult-onset-hearing-loss
#17
Ashley L Schormans, Brian L Allman
The ability to accurately integrate or bind stimuli from more than one sensory modality is highly dependent on the features of the stimuli, such as their intensity and relative timing. Previous studies have demonstrated that the ability to perceptually bind stimuli is impaired in various clinical conditions such as autism, dyslexia, schizophrenia, as well as aging. However, it remains unknown if adult-onset hearing loss, separate from aging, influences audiovisual temporal acuity. In the present study, rats were trained using appetitive operant conditioning to perform an audiovisual temporal order judgment (TOJ) task or synchrony judgment (SJ) task in order to investigate the nature and extent that audiovisual temporal acuity is affected by adult-onset hearing loss, with a specific focus on the time-course of perceptual changes following loud noise exposure...
2018: Frontiers in Behavioral Neuroscience
https://read.qxmd.com/read/30404997/social-behavior-neuroimmune-markers-and-glutamic-acid-decarboxylase-levels-in-a-rat-model-of-valproic-acid-induced-autism
#18
Tin-Tin Win-Shwe, Nay Chi Nway, Motoki Imai, Thet-Thet Lwin, Ohn Mar, Hidehiro Watanabe
Autism is a complex neurodevelopmental disorder characterized by impaired social communication and social interactions, and repetitive behaviors. The etiology of autism remains unknown and its molecular basis is not yet well understood. Pregnant Sprague-Dawley (SD) rats were administered 600 mg/kg of valproic acid (VPA) by intraperitoneal injection on day 12.5 of gestation. Both 11- to 13-week-old male and female rat models of VPA-induced autism showed impaired sociability and impaired preference for social novelty as compared to the corresponding control SD rats...
2018: Journal of Toxicological Sciences
https://read.qxmd.com/read/30367955/sex-and-region-specific-differences-in-microglia-phenotype-and-characterization-of-the-peripheral-immune-response-following-early-life-infection-in-neonatal-male-and-female-rats
#19
Brittany F Osborne, Alexandra Turano, Jasmine I Caulfield, Jaclyn M Schwarz
Early-life infection has been shown to have profound effects on the brain and behavior across the lifespan, a phenomenon termed "early-life programming". Indeed, many neuropsychiatric disorders begin or have their origins early in life and have been linked to early-life immune activation (e.g. autism, ADHD, and schizophrenia). Furthermore, many of these disorders show a robust sex bias, with males having a higher risk of developing early-onset neurodevelopmental disorders. The concept of early-life programming is now well established, however, it is still unclear how such effects are initiated and then maintained across time to produce such a phenomenon...
October 24, 2018: Neuroscience Letters
https://read.qxmd.com/read/30367913/vitamin-d3-deficiency-in-puberty-rats-causes-presynaptic-malfunctioning-through-alterations-in-exocytotic-release-and-uptake-of-glutamate-gaba-and-expression-of-eaac-1-gat-3-transporters
#20
Natalia Krisanova, Natalia Pozdnyakova, Artem Pastukhov, Marina Dudarenko, Oksana Maksymchuk, Petro Parkhomets, Roman Sivko, Tatiana Borisova
Recent experimental and epidemiologic investigations have revealed that the central nervous system is a target for vitamin D3 action and also linked vitamin D3 deficiency to Alzheimer's and Parkinson's disease, autism and dementia. Abnormal homeostasis of glutamate and GABA and signaling disbalance are implicated in the pathogenesis of major neurological diseases. Here, key transport characteristics of glutamate and GABA were analysed in presynaptic nerve terminals (synaptosomes) isolated from the cortex of vitamin D3 deficient (VDD) rats...
October 25, 2018: Food and Chemical Toxicology
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