In vivo, it has been used to identify the “birthdate” of cells during development, to examine the fate of postnatally generated cells, and to label cells before transplantation, for subsequent identification.
Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism.
Furthermore, functional brain-imaging studies have recently revealed that symptoms of ASD may be related to microanatomical abnormalities, especially dysfunction in the cortical regions (Stigler 2008).
However, the precise mechanism for the pathology of ASD is not known.
Valproic acid (VPA) has been widely used as a first-line antiepileptic drug and for the therapy of bipolar disorders for several years (Henry, 2003).
The mechanism of action is not fully understood, but it may be related, at least in part, to reduced neuronal activity by blocking sodium and calcium channels, and by enhancing the function of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) as a GABA transaminase inhibitor in human brain (Gould 2001).
In addition, previous post-mortem and neuroanatomical imaging studies of patients with autism have highlighted abnormal structures of the cerebellum, amygdala, brainstem and limbic system (Courchesne, 1997).Autism spectrum disorders (ASD) are a range of complex neurodevelopmental disorders characterized by severe impairments in reciprocal social interaction, language, and communication and by restricted, repetitive and stereotyped behaviour patterns (Geschwind & Levitt, 2007; Persico & Bourgeron, 2006).Although genetics have been believed to play a prominent role in the cause of ASD, to date, no specific genes or combination of genes have been consistently associated with the conditions.On average, 12–14 pups were obtained from VPA- VPD- and vehicle-treated mothers.Malformed pups were born at a rate of 30–40% from mothers treated with VPA at 9 d gestation.We further examined whether prenatal exposure to valpromide (VPD), a VPA analog lacking HDAC inhibition activity, induces behavioural alterations, morphological changes and hyperacetylated levels of the histones H3 and H4 in order to clarify the role of HDAC inhibition in the VPA-induced effects.Reagents were obtained from the following sources: 2-propylpentanoic acid (valproic acid; VPA) sodium salt (Sigma-Aldrich Co.Bromodeoxyuridine, variously abbreviated as Brd U, Bud R, and Brd Urd, is a halogenated thymidine analog that is permanently integrated into the DNA of dividing cells during DNA synthesis in S phase.Brd U can be immunocytochemically detected in vitro and in vivo, allowing the identification of cells that were dividing the period of Brd U exposure.In addition, clinical studies of children suggest that exposure to VPA (2001) proposed that inhibition of HDAC might be involved in VPA-induced birth defects and the efficacy of VPA in the treatment of bipolar disorder.Rodents, prenatally exposed to VPA, that exhibit some behavioural impairments similar to the features of autism are considered to be an animal model of autism (Roullet 2006).