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VPA and autism

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https://www.readbyqxmd.com/read/29116187/a-translational-study-on-looming-evoked-defensive-response-and-the-underlying-subcortical-pathway-in-autism
#1
Yu Hu, Zhuoming Chen, Lu Huang, Yue Xi, Bingxiao Li, Hong Wang, Jiajian Yan, Tatia M C Lee, Qian Tao, Kwok-Fai So, Chaoran Ren
Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29112191/identifying-specific-prefrontal-neurons-that-contribute-to-autism-associated-abnormalities-in-physiology-and-social-behavior
#2
A C Brumback, I T Ellwood, C Kjaerby, J Iafrati, S Robinson, A T Lee, T Patel, S Nagaraj, F Davatolhagh, V S Sohal
Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29093634/valproic-acid-induces-telomerase-reverse-transcriptase-expression-during-cortical-development
#3
Ki Chan Kim, Chang Soon Choi, Edson Luck T Gonzales, Darine Froy N Mabunga, Sung Hoon Lee, Se Jin Jeon, Ram Hwangbo, Minha Hong, Jong Hoon Ryu, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
The valproic acid (VPA)-induced animal model is one of the most widely utilized environmental risk factor models of autism. Autism spectrum disorder (ASD) remains an insurmountable challenge among neurodevelopmental disorders due to its heterogeneity, unresolved pathological pathways and lack of treatment. We previously reported that VPA-exposed rats and cultured rat primary neurons have increased Pax6 expression during post-midterm embryonic development which led to the sequential upregulation of glutamatergic neuronal markers...
October 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29073621/sexually-dimorphic-epigenetic-regulation-of-brain-derived-neurotrophic-factor-in-fetal-brain-in-the-valproic-acid-model-of-autism-spectrum-disorder
#4
Melissa A Konopko, Allison L Densmore, Bruce K Krueger
Prenatal exposure to the antiepileptic, mood-stabilizing drug, valproic acid (VPA), increases the incidence of autism spectrum disorders (ASDs); in utero administration of VPA to pregnant rodents induces ASD-like behaviors such as repetitive, stereotyped activity, and decreased socialization. In both cases, males are more affected than females. We previously reported that VPA, administered to pregnant mice at gestational day 12.5, rapidly induces a transient, 6-fold increase in BDNF (brain-derived neurotrophic factor) protein and mRNA in the fetal brain...
October 27, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29038507/changes-in-brain-metabolic-connectivity-underlie-autistic-like-social-deficits-in-a-rat-model-of-autism-spectrum-disorder
#5
Hojin Cho, Chul Hoon Kim, Elizabeth Quattrocki Knight, Hye Won Oh, Bumhee Park, Dong Goo Kim, Hae-Jeong Park
The neurobiological basis of social dysfunction and the high male prevalence in autism spectrum disorder (ASD) remain poorly understood. Although network alterations presumably underlie the development of autistic-like behaviors, a clear pattern of connectivity differences specific to ASD has not yet emerged. Because the heterogeneous nature of ASD hinders investigations in human subjects, we explored brain connectivity in an etiologically homogenous rat model of ASD induced by exposure to valproic acid (VPA) in utero...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28942000/oxytocin-attenuates-deficits-in-social-interaction-but-not-recognition-memory-in-a-prenatal-valproic-acid-induced-mouse-model-of-autism
#6
Yuta Hara, Yukio Ago, Momoko Higuchi, Shigeru Hasebe, Takanobu Nakazawa, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments...
September 28, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28911243/an-investigation-of-a-video-based-preference-assessment-of-social-interactions
#7
Katie Wolfe, S Shanun Kunnavatana, Adrianna M Shoemaker
We examined the use of a paired-stimulus, video-based preference assessment (VPA) to identify high- and low-preference social interactions for three children with autism spectrum disorder. We conducted two VPAs with each participant: one with access to the interaction contingent on each selection and one without access. We also conducted a concurrent-operant reinforcer assessment to evaluate the accuracy of the VPAs in identifying reinforcers. For two participants, the VPAs corresponded strongly and the results of the reinforcer assessment suggest that the high-preference interaction produced more of the target response than the low-preference interaction...
September 1, 2017: Behavior Modification
https://www.readbyqxmd.com/read/28889839/laser-acupuncture-at-ht7-improves-the-cerebellar-disorders-in-valproic-acid-rat-model-of-autism
#8
Jurairat Khongrum, Jintanaporn Wattanathorn
The novel therapeutic strategy against autism is essential due to the limited therapeutic efficacy. Based on the benefit of laser acupuncture at HT7 acupoint on the neurological disorders related with oxidative stress and inflammation, its benefit on oxidative stress, neuroinflammation, and GABAergic/glutamatergic imbalance in cerebellum of autism have been considered. To elucidate this issue, male rat pups were induced autistic-like conditions by valproic acid (VPA) and treated with laser acupuncture at HT7 acupoint once daily between postnatal Day 14 and Day 40...
August 2017: Journal of Acupuncture and Meridian Studies
https://www.readbyqxmd.com/read/28803955/valproic-acid-exposure-decreases-the-mrna-stability-of-bcl-2-via-up-regulating-mir-34a-in-the-cerebellum-of-rat
#9
Xufang Dai, Yunhou Yin, Liyan Qin
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, limited verbal communication and repetitive behaviors. Previous studies have shown that the level of Bcl-2 in the brain tissues of ASD patients is significantly decreased. However, the mechanisms underlie the down-regulation of Bcl-2 in ASD is still unknown. In this study, we investigated the alteration of Bcl-2 level and associated mechanisms in valproic acid (VPA) exposed ASD rats. VPA exposure resulted in ASD-like behaviors in rats, such as repetitive behavior and social interaction impairment...
August 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28798977/risperidone-and-aripiprazole-alleviate-prenatal-valproic-acid-induced-abnormalities-in-behaviors-and-dendritic-spine-density-in-mice
#10
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...
November 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28733898/d-cycloserine-ameliorates-autism-like-deficits-by-removing-glua2-containing-ampa-receptors-in-a-valproic-acid-induced-rat-model
#11
Han-Fang Wu, Po See Chen, Ya-Ting Hsu, Chi-Wei Lee, Tzu-Feng Wang, Yi-Ju Chen, Hui-Ching Lin
Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala. NMDAR partial agonist D-cycloserine (DCS) has been reported to act as a cognitive enhancer by increasing the NMDAR response to improve autistic-like phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is still unknown. Using combined behavioral, electrophysiological, and molecular approaches, we found that DCS administration rescued social interaction deficits and anxiety/repetitive-like behaviors observed in VPA-exposed offspring...
July 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28711654/involvement-of-endoplasmic-reticulum-stress-and-neurite-outgrowth-in-the-model-mice-of-autism-spectrum-disorder
#12
Koichi Kawada, Seisuke Mimori, Yasunobu Okuma, Yasuyuki Nomura
Neurodevelopmental disorders are congenital impairments, impeding the growth and development of the central nervous system. These disorders include autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder in Diagnostic and Statistical Manual of Mental Disorders-5. ASD is caused by a gene defect and chromosomal duplication. Despite numerous reports on ASD, the pathogenic mechanisms are not clear. The optimal methods to prevent ASD and to treat it are also not clear. Other studies have reported that endoplasmic reticulum (ER) stress contributes to the pathogenesis of neurodegenerative diseases...
July 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28687613/valproic-acid-induces-aberrant-development-of-striatal-compartments-and-corticostriatal-pathways-in-a-mouse-model-of-autism-spectrum-disorder
#13
Hsiao-Ying Kuo, Fu-Chin Liu
The striatum comprises two neurochemical compartments: striosomes and the matrix. Striosomal and matrix compartments receive inputs from limbic system-related and sensorimotor cortices, respectively. Here, we investigate the impact on the corticostriosomal pathway in the valproic acid (VPA)-induced autism spectrum disorder mouse model. VPA administration during the neurogenesis time windows of striosomes, but not the matrix, resulted in aberrant compartmentation [i.e., maternal VPA injections at embryonic day (E)12...
October 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28670439/prenatal-exposure-to-valproic-acid-increases-mir-132-levels-in-the-mouse-embryonic-brain
#14
Yuta Hara, Yukio Ago, Erika Takano, Shigeru Hasebe, Takanobu Nakazawa, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
BACKGROUND: MicroRNAs, small non-coding RNAs, are highly expressed in the mammalian brain, and the dysregulation of microRNA levels may be involved in neurodevelopmental disorders such as autism spectrum disorder (ASD). In the present study, we examined whether prenatal valproic acid (VPA) exposure affects levels of microRNAs, especially the brain specific and enriched microRNAs, in the mouse embryonic brain. RESULTS: Prenatal exposure to VPA at E12.5 immediately increased miR-132 levels, but not miR-9 or miR-124 levels, in the male embryonic brain...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28655565/environmental-enrichment-attenuates-behavioral-abnormalities-in-valproic-acid-exposed-autism-model-mice
#15
Hiroshi Yamaguchi, Yuta Hara, Yukio Ago, Erika Takano, Shigeru Hasebe, Takanobu Nakazawa, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment...
June 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28635121/exposure-to-sodium-valproate-during-pregnancy-facial-features-and-signs-of-autism
#16
Rachel Stadelmaier, Hanah Nasri, Curtis K Deutsch, Margaret Bauman, Anne Hunt, Christopher J Stodgell, Jane Adams, Lewis B Holmes
BACKGROUND: Valproic acid (VPA) is the most teratogenic anticonvulsant drug in clinical use today. Children exposed prenatally to VPA have previously been shown to have dysmorphic craniofacial features, identified subjectively but not by anthropometric methods. Exposure to VPA has also been associated with an increased frequency of autism spectrum disorder (ASD). An increased cephalic index (the ratio of the cranial lateral width to the cranial anterior-posterior length) has been observed in children with ASD...
August 15, 2017: Birth defects research
https://www.readbyqxmd.com/read/28627665/n-acetylcysteine-ameliorates-repetitive-stereotypic-behavior-due-to-its-antioxidant-properties-without-activation-of-the-canonical-wnt-pathway-in-a-valproic-acid-induced-rat-model-of-autism
#17
Yinghua Zhang, Weigang Cui, Qianqian Zhai, Tianran Zhang, Xiaojun Wen
N-acetylcysteine (NAC) is widely used as an antioxidant, and previous studies have suggested that it may have potential as an alternative therapeutic strategy for the treatment of patients with autism. However, the exact effects of NAC administration on the development of autism, as well as the molecular mechanisms underlying its actions, have yet to be fully elucidated. The present study aimed to investigate the effects of NAC on the oxidative status of rats in a valproic acid (VPA)‑induced model of autism, and to examine the involvement of the canonical Wnt signaling pathway in the actions of NAC...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28612411/deficits-in-temporal-processing-in-mice-prenatally-exposed-to-valproic-acid
#18
Julieta Acosta, Marcos A Campolongo, Christian Höcht, Amaicha M Depino, Diego A Golombek, Patricia V Agostino
Temporal processing in the seconds-to-minutes range, known as interval timing, is a crucial cognitive function that requires activation of cortico-striatal circuits via dopaminergic-glutamatergic pathways. In humans, both children and adults with autism spectrum disorders (ASD) present alterations in their estimation of time intervals. At present, there are no records of interval timing studies in animal models of ASD. Hence, the objective of the present work was to evaluate interval timing in a mouse model of prenatal exposure to valproic acid (VPA) - a treatment used to induce human-like autistic features in rodent models...
June 14, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28609577/cerebrolysin-prevents-deficits-in-social-behavior-repetitive-conduct-and-synaptic-inhibition-in-a-rat-model-of-autism
#19
Roberto Cuevas-Olguin, Swagata Roychowdhury, Anwesha Banerjee, Francisco Garcia-Oscos, Eric Esquivel-Rendon, María Elena Bringas, Michael P Kilgard, Gonzalo Flores, Marco Atzori
Autism spectrum disorder (ASD) is a syndrome of diverse neuropsychiatric diseases of growing incidence characterized by repetitive conduct and impaired social behavior and communication for which effective pharmacological treatment is still unavailable. While the mechanisms and etiology of ASD are still unknown, a consensus is emerging about the synaptic nature of the syndrome, suggesting a possible avenue for pharmacological treatment with synaptogenic compounds. The peptidic mixture cerebrolysin (CBL) has been successfully used during the last three decades in the treatment of stroke and neurodegenerative disease...
June 13, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28590943/suppressed-play-behaviour-and-decreased-oxytocin-receptor-binding-in-the-amygdala-after-prenatal-exposure-to-low-dose-valproic-acid
#20
Freja Bertelsen, Davide Folloni, Arne Møller, Anne M Landau, Jørgen Scheel-Krüger, Michael Winterdahl
To better understand the role of the neuropeptide oxytocin in autism spectrum disorder (ASD), we investigated potential deficits in social play behaviour and oxytocin receptor (OXTR) density alterations in the amygdala in a rodent model of ASD. Pregnant rats were injected daily with 20 or 100 mg/kg valproic acid (VPA) or saline from day 12 until the end of pregnancy. The number of pinning and pouncing events was assessed at postnatal days 29-34. Brains from male offspring (n=7/group) were removed at postnatal day 50...
September 2017: Behavioural Pharmacology
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