Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism

Takuma, Kazuhiro; Hara, Yuta; Kataoka, Shunsuke; Kawanai, Takuya; Maeda, Yuko; Watanabe, Ryoji; Takano, Erika; Hayata‐Takano, Atsuko; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Takehisa

doi:10.1016/j.pbb.2014.08.013

Cited by 108 publications

(77 citation statements)

References 40 publications

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“…In addition, high doses of the monocarboxylic HDAC inhibitors propionate or valproate, administered either systemically to the mother during pregnancy or intraventricular in adulthood were repeatedly shown to induce autistic-like symptoms in animal models (Chomiak et al, 2013;Macfabe, 2012;MacFabe et al, 2011MacFabe et al, , 2007Roullet et al, 2013;Thomas et al, 2012), suggesting extreme care has to be given to evaluation of the potential use of SCFAs in treatment of ASDs. Interestingly, however, the prenatal valproate-induced mouse model could also be treated with butyrate or even valproate when given at 4 weeks of age for 5 weeks, which was accompanied by increased histone H3 acetylation in the case of butyrate (Takuma et al, 2014). In the context of the microbiome-gut-brain axis, it is important to note that this model is, along with the neurodevelopmental symptoms, associated with altered composition and activity of the microbiota as well as intestinal inflammation (de Theije et al, 2014a(de Theije et al, , 2014b.…”

Section: Histone Acetylation In Psychiatric Disordersmentioning

confidence: 99%

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

Stilling

Wouw

Clarke

et al. 2016

Neurochemistry International

625

455

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Section: Histone Acetylation In Psychiatric Disordersmentioning

confidence: 99%

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

Stilling

Wouw

Clarke

et al. 2016

Neurochemistry International

625

455

View full text Add to dashboard Cite

“…At the epigenetic levels, NaB is a well-established HDAC inhibitor, suggesting that inhibition of these HDACs is likely involved in the molecular and behavioral effects. In general, it has been reported that HDAC inhibitors have potential to serve as therapeutics to treat learning and memory deficits (Takuma et al, 2014), depression (Wei et al, 2014) and cognition deficits (Graff and Tsai, 2013). …”

Section: Discussionmentioning

confidence: 99%

Valproate and sodium butyrate attenuate manganese-decreased locomotor activity and astrocytic glutamate transporters expression in mice

et al. 2018

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Manganese (Mn) is an essential trace element, but chronic overexposure to this metal, either environmentally or occupationally may cause manganism, a disease analogous to Parkinson’s disease. Inhibitors of histone deacetylases, such as valproic acid (VPA) and sodium butyrate (NaB) exert neuroprotective effects in various animal models of neurological disorders. Thus, the present study investigated whether VPA or NaB prevent Mn-induced neurotoxicity by assessing locomotor activities and expression of astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST), in C57BL/6 mice. C57BL/6 mice were pretreated with VPA (200 mg/kg, i.p.) or NaB (1200 mg/kg, i.p.) prior to intranasal instillation of Mn (30 mg/kg) continually for 21 days, followed by open-field and rota-rod behavioral tests and analyses of astrocytic glutamate transporters GLT-1 and GLAST protein/mRNA levels. The results showed that Mn significantly decreased locomotor activity as determined by total distance travelled, stereotypic and ambulatory counts. Mn also significantly decreased rota-rod activity reflecting altered motor coordination. Pretreatment with VPA and NaB with Mn reversed the effects of Mn on the locomotor activity and motor coordination. VPA and NaB also attenuated the Mn-induced decrease in GLT-1 and GLAST mRNA and protein levels in the cerebral cortical and cerebellar regions of mice. These results suggest that VPA and NaB exert protective effects against Mn toxicity seem in vitro are also shown in vivo. VPA and NaB pretreatment in mice enhancing astrocytic glutamate transporter GLT-1 expression as well as locomotor activities. Future research endeavors are warranted to determine if the therapeutic potential of VPA and NaB is via common molecular mechanism, namely, inhibition of histone deacetylases.

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“…6). When cells were transfected with Nlgn1 siRNA or a negative control siRNA using Accell siRNA the hippocampus [28] and cerebral cortex [unpublished observation]. Therefore, the present study was designed to examine the effects of prenatal HDAC inhibition on cellular maturation in primary cortical neurons from mouse embryonic cerebral cortices.…”

Section: Effect Of Nlgn1 Knockdown On Maturation Of Primary Cortical mentioning

confidence: 99%

Prenatal Exposure to Histone Deacetylase Inhibitors Affects Gene Expression of Autism-Related Molecules and Delays Neuronal Maturation

et al. 2016

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Valproic acid (VPA) is a multi-target drug and an inhibitor of histone deacetylase (HDAC). We have previously demonstrated that prenatal exposure to VPA at embryonic day 12.5 (E12.5), but not at E14.5, causes autism-like behavioral abnormalities in male mouse offspring. We have also found that prenatal VPA exposure causes transient histone hyperacetylation in the embryonic brain, followed by decreased neuronal cell numbers in the prefrontal and somatosensory cortices after birth. In the present study, we examined whether prenatal HDAC inhibition affects neuronal maturation in primary mouse cortical neurons. Pregnant mice were injected intraperitoneally with VPA (500 mg/kg) and the more selective HDAC inhibitor trichostatin A (TSA; 500 µg/kg) at E12.5 or E14.5, and primary neuronal cultures were prepared from the cerebral cortices of their embryos. Prenatal exposure to VPA at E12.5, but not at E14.5, decreased total number, total length, and complexity of neuronal dendrites at 14 days in vitro (DIV). The effects of VPA weakened at 21 DIV. Exposure to TSA at E12.5, but not at E14.5, also delayed maturation of cortical neurons. In addition, real-time quantitative PCR revealed that the prenatal exposure to TSA decreased neuroligin-1 (Nlgn1), Shank2, and Shank3 mRNA levels and increased contactin-associated protein-like 2 mRNA level. The delay in neuronal maturation was also observed in Nlgn1-knockdown cells, which were transfected with Nlgn1 siRNA. These findings suggest that prenatal HDAC inhibition causes changes in gene expression of autism-related molecules linked to a delay of neuronal maturation.

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Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism

Cited by 108 publications

References 40 publications

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

Valproate and sodium butyrate attenuate manganese-decreased locomotor activity and astrocytic glutamate transporters expression in mice

Prenatal Exposure to Histone Deacetylase Inhibitors Affects Gene Expression of Autism-Related Molecules and Delays Neuronal Maturation

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