scholarly journals Environmental Factors in the Aetiology of Autism – Lessons from Animals Prenatally Exposed to Valproic Acid

10.5772/20391 ◽  
2011 ◽  
Author(s):  
Tomasz Schneider ◽  
Ryszard Przewocki
Keyword(s):  
Valproic Acid ◽  
Environmental Factors ◽  
Prenatally Exposed

Early Behavioral Alterations and Increased Expression of Endogenous Retroviruses Are Inherited Across Generations in Mice Prenatally Exposed to Valproic Acid

2018 ◽  
Vol 56 (5) ◽  
pp. 3736-3750 ◽  
Author(s):  
Anna Maria Tartaglione ◽  
Chiara Cipriani ◽  
Flavia Chiarotti ◽  
Benedetta Perrone ◽  
Emanuela Balestrieri ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Endogenous Retroviruses ◽  
Prenatally Exposed ◽  
Behavioral Alterations

Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of NMDA receptor function

2019 ◽  
Vol 237 (1) ◽  
pp. 199-208 ◽  
Author(s):  
Somayeh Mohammadi ◽  
Majid Asadi-Shekaari ◽  
Mohsen Basiri ◽  
Mahdieh Parvan ◽  
Mohammad Shabani ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Nmda Receptor ◽  
Receptor Function ◽  
Prenatally Exposed ◽  
Adult Rats ◽  
Nmda Receptor Function

scholarly journals Kappa Opioid Receptor-mediated Modulation of Social Responding in Adolescent Rats and in Rats Prenatally Exposed to Valproic Acid

Neuroscience ◽  
2020 ◽  
Vol 444 ◽  
pp. 9-18
Author(s):  
Edel M. Hughes ◽  
Aoife M. Thornton ◽  
Daniel M Kerr ◽  
Karen Smith ◽  
Connie Sanchez ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Prenatally Exposed ◽  
Kappa Opioid ◽  
Adolescent Rats ◽  
Social Responding

Spinal nerve defects in mouse embryos prenatally exposed to valproic acid

2016 ◽  
Vol 93 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Juramt Bold ◽  
Hiromi Sakata-Haga ◽  
Yoshihiro Fukui
Keyword(s):  
Valproic Acid ◽  
Spinal Nerve ◽  
Mouse Embryos ◽  
Prenatally Exposed

scholarly journals Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2709
Author(s):  
Angel A. Puig-Lagunes ◽  
Jorge Manzo ◽  
Luis Beltrán-Parrazal ◽  
Consuelo Morgado-Valle ◽  
Rebeca Toledo-Cárdenas ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Clonic Seizure ◽  
Autism Spectrum ◽  
Seizure Susceptibility ◽  
Prenatally Exposed ◽  
Seizure Severity ◽  
Pregnant Females ◽  
Rat Pups ◽  
Spectrum Disorders ◽  
And Control

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). Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

scholarly journals Valproic Acid Induces Autism-Like Synaptic and Behavioral Deficits by Disrupting Histone Acetylation of Prefrontal Cortex ALDH1A1 in Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Huan Liu ◽  
Mei Tan ◽  
Boli Cheng ◽  
Si Wang ◽  
Lu Xiao ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Prefrontal Cortex ◽  
Histone Acetylation ◽  
Epigenetic Modification ◽  
Long Term Potentiation ◽  
Prenatally Exposed ◽  
Aldh Activity ◽  
Behavioral Deficits ◽  
Expression Levels ◽  
The Impact

ObjectivesThis study aimed to investigate the impact of valproic acid (VPA) on the histone acetylation of acetaldehyde dehydrogenase 1A1 (ALDH1A1) and the mechanism underlying VPA-induced autism-like behavior.MethodsFemale Sprague-Dawley rats were intraperitoneally injected with VPA during gestation to establish an autism model in their offspring. Some offspring prenatally exposed to VPA were randomly treated with MS-275, one histone deacetylase (HDAC) inhibitor, or retinoic acid (RA) after birth. Behavioral tests were conducted on the offspring 6 weeks after birth. Electrophysiological experiments were performed to investigate long-term potentiation (LTP) in the prefrontal cortex (PFC). The expression levels of AMPA receptors (GluA1 and 2), NMDA receptors (GluN1 and 2), synapsin 1 (SYN1), HDAC, acetylated histone 3 (AcH3), RA receptor alpha (RARα), and ALDH1A1 in the PFC were measured by Western blotting and quantitative polymerase chain reaction. ALDH enzyme activity in PFC tissue was detected using a Micro ALDH Assay Kit. The RA level in the PFC was measured using ultrahigh-performance liquid chromatography/tandem mass spectrometry. A chromatin immunoprecipitation (ChIP) experiment explored the interaction between the ALDH1A1 gene and AcH3.ResultsOffspring prenatally exposed to VPA showed autism-like behavior, upregulated the levels of LTP and GluN2A, GluA1, and SYN1 proteins relevant to synaptic plasticity in the PFC. The expression levels of HDAC3 mRNA and protein were increased. On the other hand, there was a significant reduction in the levels of AcH3, RARα, RA, ALDH1A1 mRNA and protein, the level of ALDH activity and AcH3 enrichment in the ALDH1A1 promoter region in VPA-induced offspring. Administration of MS-275 in VPA offspring significantly elevated the levels of AcH3, ALDH1A1 mRNA and protein, ALDH activity, RA, the level of RARα protein and the binding of AcH3 to the ALDH1A1 promoter. In addition, the GluA1 protein level and LTP were reduced, and most behavioral deficits were reversed. After RA supplementation in the VPA-treated offspring, the RA and RARα protein levels were significantly upregulated, GluA1 protein and LTP were downregulated, and most autism-like behavioral deficits were effectively reversed.ConclusionThese findings suggest that VPA impairs histoneacetylation of ALDH1A1 and downregulates the RA-RARα pathway. Such epigenetic modification of ALDH1A1 by VPA leads to autism-like synaptic and behavioral deficits.

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