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VPA and autism

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https://www.readbyqxmd.com/read/27878518/comparative-efficacy-of-alpha-linolenic-acid-and-gamma-linolenic-acid-to-attenuate-valproic-acid-induced-autism-like-features
#1
Sneha Yadav, Virendra Tiwari, Manjari Singh, Rajnish K Yadav, Subhadeep Roy, Uma Devi, Swetlana Gautam, Jitendra Kumar Rawat, Mohd Nazam Ansari, Abdulaziz Sa Saeedan, Anand Prakash, Shubhini A Saraf, Gaurav Kaithwas
The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups. The pups were scrutinized on the accounts of behavioral, biochemical, and inflammatory markers, and the results suggested that the GLA can impart significant protection in comparison to ALA against VPA-induced autism features. When scrutinized histopathologically, the cerebellum of the GLA-treated animals was evident for more marked protection toward neuronal degeneration and neuronal loss in comparison to ALA...
November 22, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27819277/the-transgenerational-inheritance-of-autism-like-phenotypes-in-mice-exposed-to-valproic-acid-during-pregnancy
#2
Chang Soon Choi, Edson Luck Gonzales, Ki Chan Kim, Sung Min Yang, Ji-Woon Kim, Darine Froy Mabunga, Jae Hoon Cheong, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27717813/human-adipose-derived-stem-cells-ameliorate-repetitive-behavior-social-deficit-and-anxiety-in-a-vpa-induced-autism-mouse-model
#3
Sungji Ha, Hyunjun Park, Usman Mahmood, Jeong Chan Ra, Yoo-Hun Suh, Keun-A Chang
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display co-occurring repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on valproic acid (VPA)-induced autism model mice...
October 4, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27708559/does-prenatal-valproate-interact-with-a-genetic-reduction-in-the-serotonin-transporter-a-rat-study-on-anxiety-and-cognition
#4
Bart A Ellenbroek, Caren August, Jiun Youn
There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA) enhances the risk of developing Autism Spectrum Disorders (ASD). In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals, such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27676443/targeting-anandamide-metabolism-rescues-core-and-associated-autistic-like-symptoms-in-rats-prenatally-exposed-to-valproic-acid
#5
M Servadio, F Melancia, A Manduca, A di Masi, S Schiavi, V Cartocci, V Pallottini, P Campolongo, P Ascenzi, V Trezza
Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD...
2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27638451/agmatine-rescues-autistic-behaviors-in-the-valproic-acid-induced-animal-model-of-autism
#6
Ji-Woon Kim, Hana Seung, Ki Chan Kim, Edson Luck T Gonzales, Hyun Ah Oh, Sung Min Yang, Mee Jung Ko, Seol-Heui Han, Sourav Banerjee, Chan Young Shin
Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry...
September 14, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27614006/downregulation-of-glutamatergic-and-gabaergic-proteins-in-valproric-acid-associated-social-impairment-during-adolescence-in-mice
#7
Davor Kin-Fan Chau, Angus Yiu-Ting Choi, Wen Yang, Wing Nang Leung, Chun Wai Chan
The etiology of Autism Spectrum Disorder (ASD) remains controversial. Deficits in social communication are one of the key criteria for ASD diagnosis. Valproic acid (VPA), which is an anti-epileptic and anti-depressive drug, is one of the teratogens to cause ASD onset. Moreover, synaptic dysfunction is suggested as one of the major causative factor in VPA-induced ASD in vitro and in vivo studies. Herein, this study aimed to determine the excitatory/inhibitory synaptic mRNA and protein expression in VPA-induced autistic mice...
January 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27602061/increased-expression-of-fatty-acid-synthase-and-acetyl-coa-carboxylase-in-the-prefrontal-cortex-and-cerebellum-in-the-valproic-acid-model-of-autism
#8
Jianling Chen, Wei Wu, Yingmei Fu, Shunying Yu, Donghong Cui, Min Zhao, Yasong Du, Jijun Li, Xiaohong Li
The primary aim of the present study was to investigate alterations in enzymes associated with fatty acid synthesis, namely fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), in the prefrontal cortex and cerebellum of the valproic acid (VPA)-induced animal model of autism. In this model, pregnant rats were given a single intraperitoneal injection of VPA, and prefrontal cortex and cerebellum samples from their pups were analyzed. The results of western blotting and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that the protein and mRNA expression levels of FASN, ACC and phospho-ACC (pACC) were increased in the prefrontal cortex and cerebellum of the VPA model of autism...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27592249/pharmacological-inhibition-of-fatty-acid-amide-hydrolase-attenuates-social-behavioural-deficits-in-male-rats-prenatally-exposed-to-valproic-acid
#9
Daniel M Kerr, Aoife Gilmartin, Michelle Roche
Autism spectrum disorders are a group of neurodevelopmental disorders characterised by impaired social interaction, deficits in communication and repetitive stereotyped behaviours. The endocannabinoid system plays an important role in modulating emotionality and social responding, however there have been a paucity of studies investigating this system in autistic animal models. This study investigated the effect of inhibiting fatty acid amide hydrolyase (FAAH), the anandamide catabolic enzyme, on behavioural responding in the valproic acid (VPA) rat model of autism...
August 31, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27578017/alleviation-of-n-methyl-d-aspartate-receptor-dependent-long-term-depression-via-regulation-of-the-glycogen-synthase-kinase-3%C3%AE-pathway-in-the-amygdala-of-a-valproic-acid-induced-animal-model-of-autism
#10
Han-Fang Wu, Po See Chen, Yi-Ju Chen, Chi-Wei Lee, I-Tuan Chen, Hui-Ching Lin
The amygdala plays crucial roles in socio-emotional behavior and cognition, both of which are abnormal in autism spectrum disorder (ASD). Valproic acid (VPA)-exposed rat offspring have demonstrated ASD phenotypes and amygdala excitatory/inhibitory imbalance. However, the role of glutamatergic synapses in this imbalance remains unclear. In this study, we used a VPA-induced ASD-like model to assess glutamatergic synapse-dependent long-term depression (LTD) and depotentiation (DPT) in the amygdala. We first confirmed that the VPA-exposed offspring exhibited sociability deficits, anxiety, depression-like behavior, and abnormal nociception thresholds...
August 30, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27566479/maternal-exposure-to-valproic-acid-primarily-targets-interneurons-followed-by-late-effects-on-neurogenesis-in-the-hippocampal-dentate-gyrus-in-rat-offspring
#11
Yousuke Watanabe, Tomoaki Murakami, Masashi Kawashima, Yasuko Hasegawa-Baba, Sayaka Mizukami, Nobuya Imatanaka, Yumi Akahori, Toshinori Yoshida, Makoto Shibutani
Valproic acid (VPA) is used to establish models of experimental autism. The present study investigated the developmental exposure effect of VPA on postnatal hippocampal neurogenesis in accordance with the exposure scheme of OECD Test Guideline 426 adopted for developmental neurotoxicity. Pregnant rats were administered drinking water containing 0, 667, or 2000 ppm VPA from gestational day 6 until day 21 post-delivery. In the subgranular zone (SGZ) and granule cell layer (GCL) of offspring, the number of granule cell lineage subpopulations remained unchanged upon weaning...
August 26, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27562614/developmental-profiling-of-asd-related-shank3-transcripts-and-their-differential-regulation-by-valproic-acid-in-zebrafish
#12
Chun-Xue Liu, Xiao-Lan Peng, Chun-Chun Hu, Chun-Yang Li, Qiang Li, Xiu Xu
SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood...
November 2016: Development Genes and Evolution
https://www.readbyqxmd.com/read/27498245/a-single-low-dose-of-valproic-acid-in-late-prenatal-life-alters-postnatal-behavior-and-glutamic-acid-decarboxylase-levels-in-the-mouse
#13
Ran Wei, Qi Li, Sylvia Lam, Jana Leung, Charlton Cheung, Xiaofan Zhang, Pak Chung Sham, Siew Eng Chua, Grainne Mary McAlonan
RATIONALE: Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD). Many previous studies used relatively high doses of VPA during early pregnancy, potentially confounding interpretation because the offspring are the 'survivors' of a toxic insult. Low dose or late gestation exposure has not been widely studied. OBJECTIVES: We examined the behavioral sequelae of late gestation exposure to low dose VPA in the mouse...
November 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27423376/prenatal-exposure-to-sodium-valproate-alters-androgen-receptor-expression-in-the-developing-cerebellum-in-a-region-and-age-specific-manner-in-male-and-female-rats
#14
Miguel Perez-Pouchoulen, Marta Miquel, Paul Saft, Brenda Brug, Rebeca Toledo, Maria Elena Hernandez, Jorge Manzo
Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points...
October 2016: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/27353514/increased-anxiety-like-behaviour-and-altered-gabaergic-system-in-the-amygdala-and-cerebellum-of-vpa-rats-an-animal-model-of-autism
#15
Lucia Olexová, Peter Štefánik, Lucia Kršková
Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test...
August 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27343825/valproic-acid-exposure-sequentially-activates-wnt-and-mtor-pathways-in-rats
#16
Liyan Qin, Xufang Dai, Yunhou Yin
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, limited verbal communication and repetitive behaviors. Recent studies have demonstrated that Wnt signaling and mTOR signaling play important roles in the pathogenesis of ASD. However, the relationship of these two signaling pathways in ASD remains unclear. RESULTS: We assessed this question using the valproic acid (VPA) rat model of autism. Our results demonstrated that VPA exposure activated mTOR signaling and suppressed autophagy in the prefrontal cortex, hippocampus and cerebellum of autistic model rats, characterized by enhanced phospho-mTOR and phospho-S6 and decreased Beclin1, Atg5, Atg10, LC3-II and autophagosome formation...
September 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27337090/postnatal-behavioral-and-inflammatory-alterations-in-female-pups-prenatally-exposed-to-valproic-acid
#17
Nadia Kazlauskas, Marcos Campolongo, Luciana Lucchina, Cecilia Zappala, Amaicha Mara Depino
In Autism Spectrum Disorders (ASD), a bias to a higher incidence in boys than in girls has been reported. With the aim to identify biological mechanisms acting in female animals that could underlie this bias, we used an extensively validated mouse model of ASD: the prenatal exposure to valproic acid (VPA). We found postnatal behavioral alterations in female VPA pups: a longer latency in righting reflex at postnatal day (P) 3, and a delay in the acquisition of the acoustic startle response. We also analyzed the density of glial cells in the prefrontal cortex, hippocampus and cerebellum, in VPA and control animals...
October 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27320472/pi3k-akt-mtor-mediated-autophagy-in-the-development-of-autism-spectrum-disorder
#18
Jun Zhang, Ji-Xiang Zhang, Qin-Liang Zhang
AIM: To investigate the association between PI3K/AKT/mTOR-mediated autophagy and the pathogenesis of autism spectrum disorder (ASD). METHODS: A sodium valproate (VPA)-induced baby rat model of ASD was built. Nine pregnant rats were randomly assigned into three groups, with three rats for each group: healthy control group, VPA group and mTOR inhibition group, receiving different drug administrations. Baby rats were grouped according to the maternal rats. Social interaction of baby rats (35days after birth) was observed and their bilateral hippocampes were sliced...
July 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27300699/prenatal-exposure-to-histone-deacetylase-inhibitors-affects-gene-expression-of-autism-related-molecules-and-delays-neuronal-maturation
#19
Takuya Kawanai, Yukio Ago, Ryo Watanabe, Aya Inoue, Atsuki Taruta, Yusuke Onaka, Shigeru Hasebe, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
Valproic acid (VPA) is a multi-target drug and an inhibitor of histone deacetylase (HDAC). We have previously demonstrated that prenatal exposure to VPA at embryonic day 12.5 (E12.5), but not at E14.5, causes autism-like behavioral abnormalities in male mouse offspring. We have also found that prenatal VPA exposure causes transient histone hyperacetylation in the embryonic brain, followed by decreased neuronal cell numbers in the prefrontal and somatosensory cortices after birth. In the present study, we examined whether prenatal HDAC inhibition affects neuronal maturation in primary mouse cortical neurons...
June 14, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27264355/distinct-defects-in-synaptic-differentiation-of-neocortical-neurons-in-response-to-prenatal-valproate-exposure
#20
Yoko Iijima, Katharina Behr, Takatoshi Iijima, Barbara Biemans, Josef Bischofberger, Peter Scheiffele
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by impairments in social interactions and stereotyped behaviors. Valproic acid (VPA) is frequently used to treat epilepsy and bipolar disorders. When taken during pregnancy, VPA increases the risk of the unborn child to develop an ASD. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Therefore, such rodent models may allow for identification of synaptic pathophysiology underlying ASD risk...
2016: Scientific Reports
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