Administration of Histone Deacetylase Inhibitor During Neonatal Period Changes Emotionality of Adult Male 129Sv Mice

Burenkova, Olga; Aleksandrova, E. A.; Zaraiskaya, I. Yu.

doi:10.1007/s10517-014-2409-0

Cited by 7 publications

(10 citation statements)

References 13 publications

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“…an animal model of ASD [36,37,40,44,57]. However, VPA exposure during early postnatal life can also induce ASD -like behavioral phenotypes in mice [35,56] and ferrets [45]. These studies indicate that VPA exposure can induce an animal model of ASD over a wide range of exposure durations, from the second trimester to infancy.…”

Section: Plos Onementioning

confidence: 81%

“…Developmental VPA exposure can induce ASD-like behavioral phenotypes, including reduced social interaction in mice [35,56], rats [36][37][38], common marmosets [57], and ferrets [45]. VPA-induced behavioral deficits might be associated with cortical dysgenesis characterized by increasing neuron numbers and cortical thickening in humans [39], mice [41,43], and rats [44].…”

Section: Discussionmentioning

confidence: 99%

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Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors

2021

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Valproic acid (VPA) treatment is associated with autism spectrum disorder in humans, and ferrets can be used as a model to test this; so far, it is not known whether ferrets react to developmental VPA exposure with gyrencephalic abnormalities. The current study characterized gyrification abnormalities in ferrets following VPA exposure during neonatal periods, corresponding to the late stage of cortical neurogenesis as well as the early stage of sulcogyrogenesis. Ferret pups received intraperitoneal VPA injections (200 μg/g of body weight) on postnatal days (PD) 6 and 7. BrdU was administered simultaneously at the last VPA injection. Ex vivo MRI-based morphometry demonstrated significantly lower gyrification index (GI) throughout the cortex in VPA-treated ferrets (1.265 ± 0.027) than in control ferrets (1.327 ± 0.018) on PD 20, when primary sulcogyrogenesis is complete. VPA-treated ferrets showed significantly smaller sulcal-GIs in the rostral suprasylvian sulcus and splenial sulcus but a larger lateral sulcus surface area than control ferrets. The floor cortex of the inner stratum of both the rostral suprasylvian and splenial sulci and the outer stratum of the lateral sulcus showed a relatively prominent expansion. Parvalbumin-positive neuron density was significantly greater in the expanded cortical strata of sulcal floors in VPA-treated ferrets, regardless of the BrdU-labeled status. Thus, VPA exposure during the late stage of cortical neurogenesis may alter gyrification, primarily in the frontal and parietotemporal cortical divisions. Altered gyrification may thicken the outer or inner stratum of the cerebral cortex by increasing parvalbumin-positive neuron density.

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Section: Plos Onementioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors

2021

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“…Prenatal and neonatal exposure to VPA induces ASD-like behavioral abnormalities in various mammalian species ( Miyazaki et al, 2005 ; Yochum et al, 2008 ; Mychasiuk et al, 2012 ; Favre et al, 2013 ; Burenkova et al, 2014 ; Yasue et al, 2018 ), including ferrets ( Krahe et al, 2016 ). These behavioral abnormalities are believed to be associated with cerebral cortical abnormalities that have been reported as the effect of developmental VPA exposure in ferrets ( Sawada et al, 2021 ) and other mammalian species ( Wood et al, 2014 ; Fujimura et al, 2016 ; Lauber et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Valproic acid (VPA), a well-known antiepileptic/anticonvulsant drug, also acts as an inhibitor of histone deacetylases 1 and 2 ( Göttlicher et al, 2001 ; Phiel et al, 2001 ). Many studies have reported autism spectrum disorder (ASD)-like behavioral abnormalities induced by VPA exposure during prenatal and neonatal periods in various mammalian species such as mice ( Yochum et al, 2008 ; Burenkova et al, 2014 ), rats ( Miyazaki et al, 2005 ; Mychasiuk et al, 2012 ; Favre et al, 2013 ), common marmosets ( Yasue et al, 2018 ), and ferrets ( Krahe et al, 2016 ). These behavioral abnormalities are believed to be associated with cerebral cortical abnormalities caused by developmental VPA exposure ( Sabers et al, 2014 ; Wood et al, 2014 ; Fujimura et al, 2016 ; Lauber et al, 2016 ; Sawada et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The Proliferation of Dentate Gyrus Progenitors in the Ferret Hippocampus by Neonatal Exposure to Valproic Acid

2021

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Prenatal and neonatal exposure to valproic acid (VPA) is associated with human autism spectrum disorder (ASD) and can alter the development of several brain regions, such as the cerebral cortex, cerebellum, and amygdala. Neonatal VPA exposure induces ASD-like behavioral abnormalities in a gyrencephalic mammal, ferret, but it has not been evaluated in brain regions other than the cerebral cortex in this animal. This study aimed to facilitate a comprehensive understanding of brain abnormalities induced by developmental VPA exposure in ferrets. We examined gross structural changes in the hippocampus and tracked proliferative cells by 5-bromo-2-deoxyuridine (BrdU) labeling following VPA administration to ferret infants on postnatal days (PDs) 6 and 7 at 200 μg/g of body weight. Ex vivo short repetition time/time to echo magnetic resonance imaging (MRI) with high spatial resolution at 7-T was obtained from the fixed brain of PD 20 ferrets. The hippocampal volume estimated using MRI-based volumetry was not significantly different between the two groups of ferrets, and optical comparisons on coronal magnetic resonance images revealed no differences in gross structures of the hippocampus between VPA-treated and control ferrets. BrdU-labeled cells were observed throughout the hippocampus of both two groups at PD 20. BrdU-labeled cells were immunopositive for Sox2 (>70%) and almost immunonegative for NeuN, S100 protein, and glial fibrillary acidic protein. BrdU-labeled Sox2-positive progenitors were abundant, particularly in the subgranular layer of the dentate gyrus (DG), and were denser in VPA-treated ferrets. When BrdU-labeled Sox2-positive progenitors were examined at 2 h after the second VPA administration on PD 7, their density in the granular/subgranular layer and hilus of the DG was significantly greater in VPA-treated ferrets compared to controls. The findings suggest that VPA exposure to ferret infants facilitates the proliferation of DG progenitors, supplying excessive progenitors for hippocampal adult neurogenesis to the subgranular layer.

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“…Fetal alcohol spectrum disorder (FASD) and fetal valproate syndrome are neurodevelopmental disorders (Lindhout and Schmidt, 1986;May et al, 2014;Ornoy, 2009;Rihtman et al, 2013;Riley et al, 2011) characterized by behavioral and physiological abnormalities that include sensory processing deficits, which in turn are associated with deficits in social interaction and autistic behavior (Carr et al, 2010;Nanson, 1992;Rihtman et al, 2013;Stevens et al, 2013;Williams et al, 2001). While there is extensive evidence that developmental exposure to alcohol or valproic acid (VPA) can remarkably affect social interactions in rodents (Meyer and Riley, 1986;Kelly et al, 2000;Varlinskaya and Mooney, 2014;Burenkova et al, 2014;Yochum et al, 2008;Charles Lawrence et al, 2008), much less is known about the effects of these teratogenic drugs in the social behavior of gyrencephalic species. A more complex cortex leads to more sophisticated behavior, which might be even more susceptible to the effects of teratogens.…”

Section: Introductionmentioning

confidence: 99%

Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets

Krahe

Filgueiras

Medina

2016

Intl J of Devlp Neuroscience

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Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5 g/kg, i.p.), VPA (200 mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction.

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Administration of Histone Deacetylase Inhibitor During Neonatal Period Changes Emotionality of Adult Male 129Sv Mice

Cited by 7 publications

References 13 publications

Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors

Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors

The Proliferation of Dentate Gyrus Progenitors in the Ferret Hippocampus by Neonatal Exposure to Valproic Acid

Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets

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