Maternal viral infection during pregnancy impairs development of fetal serotonergic neurons

Ohkawara, Takeshi; Katsuyama, Takashi; Ida-Eto, Michiru; Narita, Naoko; Narita, Minoru

doi:10.1016/j.braindev.2014.03.007

Cited by 40 publications

(29 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The opposing valence of changes in cell bodies versus terminal fields raises the possibility that they could be compensatory. A reduction in hippocampal serotonin coupled with increased serotonin neuron number is also shared with the VPA and maternal‐viral infection models of autism [Dufour‐Rainfray et al, ; Ohkawara et al, ]. Regardless of the origin, the current results confirm and extend the reports of reduced SERT binding in the hippocampus as measured by autoradiography [Gould et al, ] and indicate a reduction in axon density contributes to this observation and that both are associated with an overall reduction in serotonin content in BTBR mice.…”

Section: Discussionsupporting

confidence: 86%

Serotonin neuron abnormalities in the BTBR mouse model of autism

Guo

Commons

2016

Autism Research

View full text Add to dashboard Cite

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile.

show abstract

Section: Discussionsupporting

confidence: 86%

Serotonin neuron abnormalities in the BTBR mouse model of autism

Guo

Commons

2016

Autism Research

View full text Add to dashboard Cite

show abstract

“…In a mouse model of maternal immune activation, Hsiao and colleagues described elevated serum 5-HT (Hsiao et al, 2013), although it is somewhat difficult to interpret serum 5-HT levels in relation to ASD, where platelet-free plasma levels appear unchanged (Anderson et al, 1987a, Anderson, 2007, Anderson et al, 2012). Other papers reported that maternal immune activation or virus exposure resulted in abnormal development of 5-HT neurons or decreased brain 5-HT levels (Miller et al, 2013b, Ohkawara et al, 2015). More epidemiological research is needed to better understand the right way to interpret these models, but substantial evidence suggests bidirectional interplay between serotonin and the immune system, including evidence that inflammation triggers increased SERT function (Baganz and Blakely, 2013).…”

Section: Mouse Models Of Asd Risk With Abnormal 5-htmentioning

confidence: 99%

The serotonin system in autism spectrum disorder: From biomarker to animal models

2016

View full text Add to dashboard Cite

Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.

show abstract

“…Recently, abnormal inflammatory cytokine secretion due to maternal infection (such as hematogenous infection with genital mycoplasma) has been found to alter the balance between pro-inflammatory and anti-inflammatory genes, leading to abnormal brain development and autism [173,174,175,176]. Maternal inflammation has further been found to alter serotonin synthesis from tryptophan within the placenta, leading to altered serotonergic axonal growth and aberrant brain development as well as autism [177,178]. Recent studies further suggest that virus interaction with Toll-like receptors (TLRs) inhibits neuronal stem cell proliferation in the neocortex, leading to behavioral dysfunction [179].…”

Section: Infectionmentioning

confidence: 99%

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

Banik

Kandilya

Ramya

et al. 2017

Genes

View full text Add to dashboard Cite

It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down’s syndrome, Rett syndrome, and later onset of neuropsychological deficits. This review comprehensively describes the recent findings in the epigenetic landscape contributing to altered molecular profiles resulting in NDs. Furthermore, we will discuss potential avenues for future research to identify diagnostic markers and therapeutic epi-drugs to reverse these abnormalities in the brain as epigenetic marks are plastic and reversible in nature.

show abstract

Maternal viral infection during pregnancy impairs development of fetal serotonergic neurons

Cited by 40 publications

References 33 publications

Serotonin neuron abnormalities in the BTBR mouse model of autism

Serotonin neuron abnormalities in the BTBR mouse model of autism

The serotonin system in autism spectrum disorder: From biomarker to animal models

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

Contact Info

Product

Resources

About