Although valproic acid (VPA), has been shown to induce neuronal differentiation of neural stem cells (NSCs), the underlying mechanisms remain poorly understood. Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is involved in the neuronal differentiation of VPA-induced NSCs. Our data demonstrated that mTOR activation not only promoted but also was necessary for the ...

The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VP...

The anticonvulsant properties of VPA (valproic acid), a branched short-chain fatty acid, were serendipitously discovered in 1963. Since then, therapeutic roles of VPA have increased to include bipolar disorder and migraine prophylaxis, and have more recently been proposed in cancer, Alzheimer's disease and HIV treatment. These numerous therapeutic roles elevate VPA to near 'panacea' level. Surp...

The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, A...

Radiation therapy is one of the most promising therapeutic strategies in unresectable esophageal squamous cell carcinoma (ESCC). The histone deacetylase (HDAC) inhibitor has been shown to enhance radiosensitivity. Valproic acid (VPA) is a well-known drug used to treat seizure disorders and epilepsy, and has been shown to inhibit HDACs. We recently reported that a clinically safe dose of VPA enh...

Oxidative stress has been associated with valproic acid (VPA) treatment, and mitochondrial dysfunction has been implicated in the pathogenesis of VPA-idiosyncratic hepatotoxicity. The present study investigated the effect of VPA and the role of GSH on oxidative stress, mitochondrial membrane potential, and toxicity in freshly isolated rat hepatocytes. Hepatocytes were isolated from Sprague-Dawl...

Valproic acid (VPA) is an established drug in the long-term therapy of seizure disorders. Recently, VPA has been associated with anticancer activity, an effect thought to be mediated through the inhibition of cellular histone deacetylase 1. We investigated the effect of various doses of VPA (0, 1.2, and 5.0 mmol/L) administered either acutely or chronically on histone acetylation, p21 gene expr...

Serum concentrations of total carnitine, free carnitine and acylcarnitine were measured in forty-one epileptic patients treated with valproic acid (VPA). Among them, 14 patients were on VPA monotherapy and 27 were on VPA polytherapy. Forty-one age and sex matched healthy normal controls were also evaluated for carnitine metabolism. The mean total and free carnitine were significantly lower in b...

Embryonic exposure to thalidomide (THAL) or valproic acid (VPA) before neural tube closure has been demonstrated as a useful model for human autism in rats. Abnormalities of the serotonergic system which are often observed in human autism have been shown in these rats. Thus, we examined whether early serotonergic neuronal development is perturbed by THAL/VPA. When pregnant rats were exposed to ...

Disorders involving dysfunctional sensory processing are characterized by an inability to filter sensory information, particularly simultaneously arriving multimodal inputs. We examined the effects of prenatal exposure to valproic acid (VPA), a teratogen linked to sensory dysfunction, on the behavior of juvenile and adult rats, and on the anatomy of the superior colliculus, a critical multisens...