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VPA and autism

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https://www.readbyqxmd.com/read/28635121/exposure-to-sodium-valproate-during-pregnancy-facial-features-and-signs-of-autism
#1
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...
June 21, 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
#2
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...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28612411/deficits-in-temporal-processing-in-mice-prenatally-exposed-to-valproic-acid
#3
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
#4
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
#5
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...
June 6, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28486989/postnatal-treatment-using-curcumin-supplements-to-amend-the-damage-in-vpa-induced-rodent-models-of-autism
#6
Maha Al-Askar, Ramesa Shafi Bhat, Manar Selim, Laila Al-Ayadhi, Afaf El-Ansary
BACKGROUND: Valproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism. METHODS: The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12...
May 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28472621/the-valproic-acid-induced-rodent-model-of-autism
#7
REVIEW
Chiara Nicolini, Margaret Fahnestock
Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children...
May 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28427452/modeling-environmental-risk-factors-of-autism-in-mice-induces-ibd-related-gut-microbial-dysbiosis-and-hyperserotonemia
#8
Joon Seo Lim, Mi Young Lim, Yongbin Choi, GwangPyo Ko
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD...
April 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28408291/altered-expression-of-circadian-rhythm-and-extracellular-matrix-genes-in-the-medial-prefrontal-cortex-of-a-valproic-acid-rat-model-of-autism
#9
Nikkie F M Olde Loohuis, Gerard J M Martens, Hans van Bokhoven, Barry B Kaplan, Judith R Homberg, Armaz Aschrafi
Autism spectrum disorders (ASD) are a highly heterogeneous group of neurodevelopmental disorders caused by complex interplay between various genes and environmental factors during embryonic development. Changes at the molecular, cellular and neuroanatomical levels are especially evident in the medial prefrontal cortex (mPFC) of ASD patients and are particularly contributing to social impairments. In the present study we tested the hypothesis that altered neuronal development and plasticity, as seen in the mPFC of ASD individuals, may result from aberrant expression of functionally connected genes...
April 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28360521/rapamycin-modulated-brain-derived-neurotrophic-factor-and-b-cell-lymphoma-2-to-mitigate-autism-spectrum-disorder-in-rats
#10
Jie Zhang, Li-Ming Liu, Jin-Feng Ni
The number of children suffered from autism spectrum disorder (ASD) is increasing dramatically. However, the etiology of ASD is not well known. This study employed mammalian target of rapamycin inhibitor rapamycin to explore its effect on ASD and provided new therapeutic strategies for ASD. ASD rat model was constructed and valproic acid (VPA) was injected intraperitoneally into rats on pregnancy day 12.5. Offspring from VPA group were divided into ASD group and ASD + rapamycin (ASD + RAPA) group. Compared with normal group, the frequency and duration of social behavior and straight times of ASD group were shortened, but the grooming times were extended...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28324861/behavioral-improvements-in-a-valproic-acid-rat-model-of-autism-following-vitamin-d-supplementation
#11
Lin Du, Guolian Zhao, Zipeng Duan, Fan Li
The aim was to identify the effects of early vitamin D supplementation on autism-like behaviors (ASD) induced by valproic acid (VPA, an anti-convulsant and a mood stabilizer) in rats. 10 male Wistar rat pups with prenatal exposure to saline were in control group, and 20 Pups with prenatal exposure to VPA were divided into ASD-N (0.9% saline treated) and ASD-D group (vitamin D 80,000 IU/kg treated) on postnatal day 12. Self-grooming, olfactory habituation/dishabituation, and social interaction tests were conducted to assess social interaction, communication, and repetitive behaviors...
March 6, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28161158/fingolimod-fty720-attenuates-social-deficits-learning-and-memory-impairments-neuronal-loss-and-neuroinflammation-in-the-rat-model-of-autism
#12
Hongmei Wu, Xuelai Wang, Jingquan Gao, Shuang Liang, Yanqiu Hao, Caihong Sun, Wei Xia, Yonggang Cao, Lijie Wu
AIMS: To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. MAIN METHODS: As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated...
March 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28147267/abnormal-development-of-the-earliest-cortical-circuits-in-a-mouse-model-of-autism-spectrum-disorder
#13
Daniel A Nagode, Xiangying Meng, Daniel E Winkowski, Ed Smith, Hamza Khan-Tareen, Vishnupriya Kareddy, Joseph P Y Kao, Patrick O Kanold
Autism spectrum disorder (ASD) involves deficits in speech and sound processing. Cortical circuit changes during early development likely contribute to such deficits. Subplate neurons (SPNs) form the earliest cortical microcircuits and are required for normal development of thalamocortical and intracortical circuits. Prenatal valproic acid (VPA) increases ASD risk, especially when present during a critical time window coinciding with SPN genesis. Using optical circuit mapping in mouse auditory cortex, we find that VPA exposure on E12 altered the functional excitatory and inhibitory connectivity of SPNs...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/27984183/repeated-prenatal-exposure-to-valproic-acid-results-in-cerebellar-hypoplasia-and-ataxia
#14
Stacey L Main, Randy J Kulesza
Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27938419/increased-gabaa-receptor-binding-in-amygdala-after-prenatal-administration-of-valproic-acid-to-rats
#15
Freja Bertelsen, Arne Møller, Davide Folloni, Kim Ryun Drasbek, Jørgen Scheel-Krüger, Anne M Landau
OBJECTIVE: Prenatal exposure to valproic acid (VPA) enhances the risk for later development of autism spectrum disorders (ASD). An altered gamma-aminobutyric acid (GABA) system may be a key factor in ASD. Here we investigated possible changes in the GABA system in rats exposed to a low dose of prenatal VPA. METHOD: We performed autoradiography with [3H]muscimol, (a GABAA receptor agonist), and [11C]Ro15-4513 (a partial agonist of the GABAA α1+5 receptor subtypes), in brain sections containing amygdala, thalamus and hippocampus of rats treated prenatally with 20 mg/kg VPA or saline from the 12th day of gestation...
December 12, 2016: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/27917314/pentylenetetrazole-induced-seizures-in-developing-rats-prenatally-exposed-to-valproic-acid
#16
Angel A Puig-Lagunes, Jorge Manzo, Luis Beltrán-Parrazal, Consuelo Morgado-Valle, Rebeca Toledo-Cárdenas, Maria-Leonor López-Meraz
BACKGROUND: Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20-25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model. METHODS: Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo)...
2016: PeerJ
https://www.readbyqxmd.com/read/27878518/comparative-efficacy-of-alpha-linolenic-acid-and-gamma-linolenic-acid-to-attenuate-valproic-acid-induced-autism-like-features
#17
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
#18
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
#19
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...
January 15, 2017: 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
#20
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
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