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VPA and autism

Mauro Mozael Hirsch, Iohanna Deckmann, Mellanie Fontes-Dutra, Guilherme Bauer-Negrini, Gustavo Della-Flora Nunes, Walquiria Nunes, Bruna Rabelo, Rudimar Riesgo, Rogerio Margis, Victorio Bambini-Junior, Carmem Gottfried
Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication and language, and restricted repertoire of activities and interests. The etiology of ASD remains unknown and no clinical markers for diagnosis were identified. Environmental factors, including prenatal exposure to valproic acid (VPA), may contribute to increased risk of developing ASD. MicroRNA (miRNA) are small noncoding RNA that regulate gene expression and are frequently linked to biological processes affected in neurodevelopmental disorders...
March 3, 2018: Food and Chemical Toxicology
Ryan Zimmerman, Raina Patel, Amanda Smith, Julio Pasos, Randy J Kulesza
Auditory dysfunction is a common occurrence in individuals with autism spectrum disorder (ASD). While most cases of ASD are of unknown etiology, in utero exposure to the antiepileptic valproic acid (VPA) significantly increases risk. We have previously identified significant dysmorphology and hypoplasia in the auditory brainstem of humans with ASD and rodents exposed to VPA in utero. Further, we have identified abnormal c-Fos immunolabeling patterns after exposure to pure tone stimuli in VPA-exposed animals...
March 3, 2018: Neuroscience
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
Luana Carvalho Cezar, Thiago Berti Kirsten, Caio Cesar Navarrete da Fonseca, Ana Paula Nascimento de Lima, Maria Martha Bernardi, Luciano Freitas Felicio
Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition. Recent studies have suggested that valproic acid (VPA), an anti-epileptic drug with teratogenic activity, is related to autism. In rodents, VPA exposure during pregnancy induces autistic-like effects. Exposure to VPA may alter zinc metabolism resulting in a transient deficiency of zinc. Therefore, we selected zinc as a prenatal treatment to prevent VPA-induced impairments in a rat model of autism...
February 23, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Ruoxin Zhang, Jinlong Zhou, Junrong Ren, Siqi Sun, Yuanyuan Di, Hanyu Wang, Xiaoqin An, Kexin Zhang, Junfeng Zhang, Zhaoqiang Qian, Meimei Shi, Yanning Qiao, Wei Ren, Yingfang Tian
Gene-environmental interaction could be the major cause of autism. The aim of the current study is to detect the effects of valproic acid on gene expression profiles and alternatively spliced genes in the prefrontal cortex in rat models of autism. Female rats received a single intraperitoneal injection of 600 mg/kg valproic acid at day 12.5 post-conception, and controls were injected with saline. Only male offspring were employed in the current study. RNA sequencing was used to investigate transcriptome in the prefrontal cortex of VPA-exposed rats...
February 7, 2018: Reproductive Toxicology
Brittany D Needham, Weiyi Tang, Wei-Li Wu
Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring...
February 7, 2018: Developmental Neurobiology
Miyuki Yasue, Akiko Nakagami, Keiko Nakagaki, Noritaka Ichinohe, Nobuyuki Kawai
Humans and various nonhuman primates respond negatively to inequity not in their favor (i.e., inequity aversion), when inequity between two individuals is introduced. Common marmosets, a highly prosocial species, further discriminated between human actors who reciprocated in social exchanges, and those who did not. Conversely, marmoset models of autism, induced via prenatal exposure to valproic acid (VPA marmosets), did not discriminate. Interestingly, previous studies of inequity aversion in marmosets have produced negative results, or were limited to males...
January 24, 2018: Behavioural Brain Research
Diego Baronio, Henri A J Puttonen, Maria Sundvik, Svetlana Semenova, Essi Lehtonen, Pertti Panula
BACKGROUND AND PURPOSE: Histamine modulates several behaviors and physiological functions and its deficiency is associated with neuropsychiatric disorders. Gestational intake of valproic acid (VPA) is linked to Autism Spectrum Disorder (ASD), which is characterized by impaired sociability and stereotypies. VPA effects on the neurochemistry and functional morphology of the histaminergic system in ASD are unclear. Zebrafish are highly social and given the similarities between zebrafish and human neurotransmitter systems, we decided to use zebrafish to study VPA effects on histamine...
December 12, 2017: British Journal of Pharmacology
Hongmei Wu, Quanzhi Zhang, Jingquan Gao, Caihong Sun, Jia Wang, Wei Xia, Yonggang Cao, Yanqiu Hao, Lijie Wu
RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. OBJECTIVE: The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism...
March 2018: Psychopharmacology
Michela Servadio, Antonia Manduca, Francesca Melancia, Loris Leboffe, Sara Schiavi, Patrizia Campolongo, Maura Palmery, Paolo Ascenzi, Alessandra di Masi, Viviana Trezza
Prenatal exposure to the antiepileptic and mood stabilizer valproic acid (VPA) is an environmental risk factor for autism spectrum disorders (ASD), although recent epidemiological studies show that the public awareness of this association is still limited. Based on the clinical findings, prenatal VPA exposure in rodents is a widely used preclinical model of ASD. However, there is limited information about the precise biochemical mechanisms underlying the link between ASD and VPA. Here, we tested the effects of increasing doses of VPA on behavioral features resembling core and secondary symptoms of ASD in rats...
January 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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
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
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
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
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
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...
November 2017: Hormones and Behavior
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
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
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
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
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