Valproic acid reduces spatial working memory and cell proliferation in the hippocampus

Umka, Jariya; Mustafa, Sarah; ELBeltagy, Maha; Thorpe, Alison; Latif, Liaque; Bennett, Gerald; Wigmore, Peter

doi:10.1016/j.neuroscience.2009.11.073

Cited by 104 publications

(123 citation statements)

References 73 publications

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“…Importantly, the decreased cell proliferation in the presence of HDAC inhibitors was accompanied by promotion of neuronal phenotypic differentiation (Hsieh et al, 2004;Jessberger et al, 2007;Umka et al, 2010;Yao et al, 2010;Zhou et al, 2011a,b;Huang et al, 2012;Liu et al, 2012) and by simultaneous up-regulation of genes such as NeuroD, SCG19, synapsin, governing differentiation towards neurons (Hao et al, 2004). By contrast, differentiation towards the oligodendrocytes and astrocytes was inhibited.…”

Section: The Involvement Of Hdac1 and Hdac2 In Neurogenesismentioning

confidence: 99%

Histone deacetylases 1 and 2 are required for brain development

Jaworska

Ziemka‐Nałęcz

Zalewska³

2015

Int. J. Dev. Biol.

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Epigenetic modifications of histones have been implicated in the regulation of cell specific expression of genes required for neuronal development. The best studied post-translational (epigenetic) modification of histones is the process of reversible acetylation. Two types of enzymeshistone acetyltransferases (HATs) and histone deacetylases (HDACs) establish and maintain specific patterns of histone acetylation in balance, thereby contributing to both transcriptional activation and repression of specific sets of genes. Histone deacetylases catalyze the removal of acetyl groups from selected lysine residues in the conserved tails of core histone proteins and are considered as transcriptional corepressors. A significant amount of data implicates HDACs in diverse biological processes, including tissue specific developmental program by silencing specific growth-inhibitory genes. In line with this, gene disruption studies have shown that the class I deacetylases, HDAC1 and HDAC2 play an essential role in nervous system development. In the present review, we briefly highlight current insights supporting the function of histone deacetylases in rodent brain development and discuss present knowledge referring to their role in neurogenesis, taking into consideration results obtained in culture systems and in in vivo studies.

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Section: The Involvement Of Hdac1 and Hdac2 In Neurogenesismentioning

confidence: 99%

Histone deacetylases 1 and 2 are required for brain development

Jaworska

Ziemka‐Nałęcz

Zalewska³

2015

Int. J. Dev. Biol.

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“…Recent studies have shown that VPA functions as a histone deacetylase inhibitor (Venkataramani et al 2010;Chen et al 2013). The inhibitory effects of VPA on histone deacetylase activity have been found to reduce cell proliferation in the rat hippocampal dentate gyrus, which may be due to decreased levels of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in the neurosphere from the subventricular zone (SVZ) of adult mice (Umka et al 2010;Zhou et al 2011). In contrast, it was recently reported that VPA exposure to pregnant mice transiently increases BDNF mRNA and protein levels in the fetal mouse brain, which may cause aberrant brain development (Almeida et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Valproic acid decreases cell proliferation and migration in the cerebellum of zebrafish larvae

Lee

2014

Animal Cells and Systems

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Valproic acid (VPA) is used as an antiepileptic drug or mood stabilizer. Recent studies have shown that exposure to VPA during embryonic development alters neural progenitor cell proliferation. The main goal of this investigation was to elucidate the effects of VPA on cell proliferation in the cerebellum of zebrafish larvae using immunohistochemistry. 5-bromo-2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA)-labeled cells were mostly found in the ventral cerebellum proliferation zone and external granular layer of the cerebellum from 5 days postfertilization zebrafish immediately after treatment with BrdU for 12 h. Subsequently, BrdU-labeled cells were mostly found in the medial zone of the cerebellar plate 48 h after terminating BrdU treatment. Pretreatment with 2-mM VPA for 3 h prior to BrdU exposure reduced the number of BrdU-labeled cells both immediately and 48 h after terminating BrdU exposure. Posttreatment with VPA following BrdU exposure reduced the migration of BrdU-labeled cells, represented by a decreased number of BrdUpositive cells in the medial zone of the cerebellar plate. These results suggest that VPA may delay brain development by hindering cell proliferation and migration during the early developmental period.

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“…A recent study demonstrated that the cognitive side effect profile of lacosamide is comparable to that of LTG and superior to that of topiramate, which was indicated by both subjective and objective measures [43]. VPA does not appear to impair cognition if sufficiently controlled for hyperammonemia [42]; however, studies have shown VPA can reduce spatial working memory and cell proliferation in the hippocampus [44]. These results support the idea that VPA may cause cognitive impairment by reducing neurogenesis within the hippocampus [44].…”

Section: Discussionmentioning

confidence: 79%

“…VPA does not appear to impair cognition if sufficiently controlled for hyperammonemia [42]; however, studies have shown VPA can reduce spatial working memory and cell proliferation in the hippocampus [44]. These results support the idea that VPA may cause cognitive impairment by reducing neurogenesis within the hippocampus [44]. In this study, the average daily dose of LTG was similar between the two IGE groups, but the patients with IEDs had a higher average daily dose of VPA compared with the patients without IEDs; however, the daily dose of VPA was used as covariant in our analysis, and we found this difference did not affect our results.…”

Section: Discussionmentioning

confidence: 97%

Impaired Executive Function by Interictal Epileptiform Discharges in Patients with Idiopathic Generalized Epilepsy

Nong¹,

Wang²

2017

Epilepsy J

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Objective: Many patients with Idiopathic Generalized Epilepsy (IGE) exhibit cognitive deficits. Interictal Epileptiform Discharges (IEDs) may contribute to cognitive impairment in epilepsy; however, the relationship between IEDs and cognitive impairment is unclear. Methods:In this study, we analysed executive function in three groups: IGE patients with IEDs, IGE patients without IEDs and healthy controls. Executive function was assessed using the Stroop Test, the Verbal Fluency Test, the Digit Span Test and Wisconsin Card-Sorting Test. Results:The IGE patients with IEDs performed worse on executive function tests compared with patients without IEDs. Furthermore, the IGE patients without IEDs performed worse compared with healthy controls. There were significant differences between the three groups in performance on the Stroop Test, the Digit Span Test (forward and backward), Verbal Fluency Test (animals, fruits) and the subscales of WCST (Categories Completed, Correct Response, Total Errors and Preservative Errors). Conclusion:These results suggest that executive function in patients with IGE is impaired and is further impaired by IEDs. Future studies should determine whether well-controlled patients with IGE could benefit from antiepileptic treatment.

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Valproic acid reduces spatial working memory and cell proliferation in the hippocampus

Cited by 104 publications

References 73 publications

Histone deacetylases 1 and 2 are required for brain development

Histone deacetylases 1 and 2 are required for brain development

Valproic acid decreases cell proliferation and migration in the cerebellum of zebrafish larvae

Impaired Executive Function by Interictal Epileptiform Discharges in Patients with Idiopathic Generalized Epilepsy

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