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Valproic acid affects neurogenesis during early optic tectum development in zebrafish.

ABSTRACT: The mammalian superior colliculus and its non-mammalian homolog, the optic tectum (OT), are midbrain structures that integrate multimodal sensory inputs and guide non-voluntary movements in response to prevalent stimuli. Recent studies have implicated this structure as a possible site affected in autism spectrum disorder (ASD). Interestingly, fetal exposure to valproic acid (VPA) has also been associated with an increased risk of ASD in humans and animal models. Therefore, we took the approach of determining the effects of VPA treatment on zebrafish OT development as a first step in identifying the mechanisms that allow its formation. We describe normal OT development during the first 5 days of development and show that in VPA-treated embryos, neuronal specification and neuropil formation was delayed. VPA treatment was most detrimental during the first 3 days of development and did not appear to be linked to oxidative stress. In conclusion, our work provides a foundation for research into mechanisms driving OT development, as well as the relationship between the OT, VPA, and ASD. This article has an associated First Person interview with one of the co-first authors of the paper.

SUBMITTER: Dixon SC

PROVIDER: S-EPMC9916031 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Valproic acid affects neurogenesis during early optic tectum development in zebrafish.

Dixon Sierra C SC Calder Bailey J BJ Lilya Shane M SM Davies Brandon M BM Martin Annalie A Peterson Maggie M Hansen Jason M JM Suli Arminda A

Biology open 20230131 1

The mammalian superior colliculus and its non-mammalian homolog, the optic tectum (OT), are midbrain structures that integrate multimodal sensory inputs and guide non-voluntary movements in response to prevalent stimuli. Recent studies have implicated this structure as a possible site affected in autism spectrum disorder (ASD). Interestingly, fetal exposure to valproic acid (VPA) has also been associated with an increased risk of ASD in humans and animal models. Therefore, we took the approach o ...[more]

PMID: 36537579

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Project description:Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance during vertebrate embryonic development.

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Valproic acid affects neurogenesis during early optic tectum development in zebrafish.

Publications

Valproic acid affects neurogenesis during early optic tectum development in zebrafish.

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