Degraded cortical temporal processing in the valproic acid-induced rat model of autism

Hearing disorders, such as abnormal speech perception, are frequently reported in autistic individuals.
However, the mechanisms underlying these auditory-associated signature deficits in autism remain largely unknown.
In this study, we documented significant behavioral impairments in the sound temporal rate discrimination task for rats prenatally exposed to valproic acid (VPA), a well-validated animal model for studying the pathology of autism. In parallel, there was a large-scale degradation in temporal information-processing in their primary auditory cortices (A1) at both levels of spiking outputs and synaptic inputs.
Substantially increased spine density of excitatory neurons and decreased numbers of parvalbumin- and somatostatin-labeled inhibitory inter-neurons were also recorded in the A1 after VPA exposure.
Given the fact that cortical temporal processing of sound is associated with speech perception in humans, these results in the animal model of VPA exposure provide insight into a possible neurological mechanism underlying auditory and language-related deficits in individuals with autism.

Meropenem to Treat Valproic Acid Intoxication

This TDM grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed.
Meropenem was administered to enhance the clearance of valproic acid.
This off-label usage of meropenem is based on the drug-drug interaction between carbapenems and valproic acid, which reduced the level of valproic acid within 24 h after administration.

Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells

Our previous study found that the level of CCN1 increases as osteogenic differentiation progresses in tonsil-derived mesenchymal stem cells (TMSCs). This study investigated how CCN1 is regulated through HDAC inhibition in TMSCs and their relationship with osteogenesis.
Valproic acid (VPA) (1-5 mM), a well-known histone deacetylase (HDAC) inhibitor, strongly inhibited TMSC proliferation without altering MSC-specific surface markers, CD14, 34, 45, 73, 90 and 105.
However, CD146 expression increased at 5 mM VPA. VPA increased osteogenic differentiation of TMSCs but decreased adipogenesis and chondrogenesis, as evidenced by the cell-specific staining of differentiation. The former was validated by the increased osteocalcin (OCN).
The changes in CCN1 by VPA was biphasic; it increased until 48 h and decreased thereafter.
Knockdown of CCN1 by using siRNA inhibited the osteogenic effect of VPA. VPA had no effect on CCN1 mRNA expression, but inhibition of protein synthesis by cycloheximide showed that VPA slowed down the CCN1 protein degradation. Moreover, overexpression of HDAC1 completely inhibited VPA-induced CCN1.
Our results indicate that VPA inhibits the HDAC1, inducing CCN1 protein stability rather than gene expression, thereby promoting osteogenic differentiation of TMSCs.
These findings present the noble implication of VPA as an inhibitor of HDAC1 to facilitate CCN1-induced osteogenic differentiation of MSCs.

Use of TLC-Densitometric Method for Determination of Valproic Acid in Capsules

Determination of valproic acid in the drug was carried out on the aluminum silica gel 60F254 plates and using acetone-water-chloroform-ethanol-ammonia at a volume ratio of 30:1:8:5:11 as the mobile phase, respectively. Two methods of detection of valproic acid were used.
The first was a 2% aqueous CuSO4×5H2O solution, and the second was a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system.
The applied TLC-densitometric method is selective, linear, accurate, precise, and robust, regardless of the visualizing reagent used for the determination of valproic acid in Convulex capsules.
It has low limits of detection (LOD) and limits of quantification (LOQ), which are equal to 5.8 μg/spot and 17.4 μg/spot using a 2% aqueous CuSO4×5H2O solution as a visualizing agent and also 0.32 μg/spot and 0.97 μg/spot using a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system as visualizing reagent, respectively.
The described analytical method can additionally be used to study the identity of valproic acid in a pharmaceutical preparation.
The linearity range was found to be 20.00-80.00 μg/spot and 1.00-2.00 μg/spot for valproic acid detected on chromatographic plates using a 2% aqueous CuSO4×5H2O solution and the 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system, respectively. A coefficient of variation that was less than 3% confirms the satisfactory accuracy and precision of the proposed method.
The results of the assay of valproic acid equal 96.2% and 97.0% in relation to the label claim that valproic acid fulfill pharmacopoeial requirements.
The developed TLC-densitometric method can be suitable for the routine analysis of valproic acid in pharmaceutical formulations.
The proposed TLC-densitometry may be an alternative method to the modern high-performance liquid chromatography and square wave voltammetry in the control of above-mentioned substances, and it can be applied when other analytical techniques is not affordable in the laboratory.

Comparative analysis of background EEG activity in juvenile myoclonic epilepsy during valproic acid treatment: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study

Background: By definition, the background EEG is normal in juvenile myoclonic epilepsy (JME) patients and not accompanied by other developmental and cognitive problems.
However, some recent studies using quantitative EEG (qEEG) reported abnormal changes in the background activity. QEEG investigation in patients undergoing anticonvulsant treatment might be a useful approach to explore the electrophysiology and anticonvulsant effects in JME.
Methods: We investigated background EEG activity changes in patients undergoing valproic acid (VPA) treatment using qEEG analysis in a distributed source model. In 17 children with JME, non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between untreated and treated conditions.
Results: VPA reduced background EEG activity in the low-frequency (delta-theta) bands across the frontal, parieto-occipital, and limbic lobes (threshold log-F-ratio = ±1.414, p < 0.05; threshold log-F-ratio= ±1.465, p < 0.01). In the delta band, comparative analysis revealed significant current density differences in the occipital, parietal, and limbic lobes. In the theta band, the analysis revealed significant differences in the frontal, occipital, and limbic lobes. The maximal difference was found in the delta band in the cuneus of the left occipital lobe (log-F-ratio = -1.840) and the theta band in the medial frontal gyrus of the left frontal lobe (log-F-ratio = -1.610).
Conclusions: This study demonstrated the anticonvulsant effects on the neural networks involved in JME. In addition, these findings suggested the focal features and the possibility of functional deficits in patients with JME.
Keywords: Distributed source model; Juvenile myoclonic epilepsy (JME); Quantitative electroencephalography (qEEG); Standardized low-resolution brain electromagnetic tomography (sLORETA); Valproic acid.

iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social and communication difficulties.
Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD. However, the mechanisms involved have not yet been determined. In this study, we used iTRAQ (isobaric tags for relative and absolute quantification) proteomics analysis of the cerebral cortex of a VPA rat model (VPA group) and controls (CON group).
The results showed that 79 differentially expressed proteins (DEPs) were identified between the VPA group and the CON group. Based on bioinformatics analysis, the DEPs were mainly enriched at synapses, especially glutamatergic synapses and GABAergic synapses. Some DEPs were involved in energy metabolism, thyroid hormone synthesis pathway, and Na+-K+-ATPase.

Valproic Acid

M41002 EpiGentek 500 mg 128.3 EUR

Valproic acid

HY-10585 MedChemExpress 10mM/1mL 113 EUR

Valproic acid

B1251-10000 ApexBio 10 g 189 EUR

Valproic acid

B1251-5.1 ApexBio 10 mM (in 1mL DMSO) 108 EUR

Valproic acid

B1251-5000 ApexBio 5 g 142 EUR

Valproic Acid [BSA]

DAG3422 Creative Diagnostics 1mg 1235 EUR

Valproic acid, > 98%

BC285-010 GenDepot 10g 138 EUR

Valproic acid, > 98%

BC285-025 GenDepot 25g 219 EUR

Valproic acid, > 98%

BC285-100 GenDepot 100g 354 EUR

Valproic Acid Antibody

abx021084-200ug Abbexa 200 ug 328 EUR

Valproic Acid antibody

10-V12A Fitzgerald 500 ug 493 EUR

Valproic acid (sodium salt)

HY-10585A MedChemExpress 10mM/1mL 113 EUR

Valproic Acid, Sodium Salt

1647-200 Biovision 158 EUR

Valproic acid sodium salt (Sodium valproate)

A4099-10000 ApexBio 10 g 189 EUR

Valproic acid sodium salt (Sodium valproate)

A4099-5.1 ApexBio 10 mM (in 1mL DMSO) 108 EUR

Valproic acid sodium salt (Sodium valproate)

A4099-5000 ApexBio 5 g 142 EUR
Cytoskeleton and endoplasmic reticulum (ER) stress-related proteins were also involved. Some DEPs matched either the ASD gene database or previous reports on cerebral cortical transcriptome studies in VPA rat models.
Dysregulation of these DEPs in the cerebral cortex of VPA rats may be responsible for autism-like behavior in rats.
We also found that some DEPs were associated with neuropsychiatric disorders, implying that these diseases share common signaling pathways and mechanisms.
Moreover, increased expression of DEPs was associated with energy metabolism in the cerebral cortex of VPA rats, implying that ASD may be a distinct type of mitochondrial dysfunction that requires further investigation.

Geef een antwoord

Het e-mailadres wordt niet gepubliceerd.