scholarly journals Long-Lasting Changes in Glial Cells Isolated From Rats Subjected to the Valproic Acid Model of Autism Spectrum Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianela Evelyn Traetta ◽  
Nonthué Alejandra Uccelli ◽  
Sandra Cristina Zárate ◽  
Dante Gómez Cuautle ◽  
Alberto Javier Ramos ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Cortical Neurons ◽  
Primary Cultures ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Saline Control ◽  
Synaptic Changes

Synaptic alterations concomitant with neuroinflammation have been described in patients and experimental models of autism spectrum disorder (ASD). However, the role of microglia and astroglia in relation to synaptic changes is poorly understood. Male Wistar rats prenatally exposed to valproic acid (VPA, 450 mg/kg, i.p.) or saline (control) at embryonic day 10.5 were used to study synapses, microglia, and astroglia in the prefrontal cortex (PFC) at postnatal days 3 and 35 (PND3 and PND35). Primary cultures of cortical neurons, microglia, and astroglia isolated from control and VPA animals were used to study each cell type individually, neuron-microglia and microglia-astroglia crosstalk. In the PFC of VPA rats, synaptic changes characterized by an increase in the number of excitatory synapses were evidenced at PND3 and persisted until PND35. At PND3, microglia and astroglia from VPA animals were morphologically similar to those of age-matched controls, whereas at PND35, reactive microgliosis and astrogliosis were observed in the PFC of VPA animals. Cortical neurons isolated from VPA rats mimicked in vitro the synaptic pattern seen in vivo. Cortical microglia and astroglia isolated from VPA animals exhibited reactive morphology, increased pro-inflammatory cytokines, and a compromised miRNA processing machinery. Microglia from VPA animals also showed resistance to a phagocytic challenge. In the presence of neurons from VPA animals, microglia isolated from VPA rats revealed a non-reactive morphology and promoted neurite outgrowth, while microglia from control animals displayed a reactive profile and promoted dendritic retraction. In microglia-astroglia co-cultures, microglia from VPA animals displayed a reactive profile and exacerbated astrocyte reactivity. Our study indicates that cortical microglia from VPA animals are insensitive or adapted to neuronal cues expressed by neurons from VPA animals. Further, long-term in vivo microgliosis could be the result of altered microglia-astroglia crosstalk in VPA animals. Thus, our study highlights cortical microglia-astroglia communication as a new mechanism implicated in neuroinflammation in ASD; consequently, we propose that this crosstalk is a potential target for interventions in this disorder.

Role of Vitamin D in Autism Spectrum Disorder

2020 ◽  
Vol 25 (41) ◽  
pp. 4357-4367 ◽  
Author(s):  
Loai Alzghoul
Keyword(s):  
Autism Spectrum Disorder ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Autism Spectrum ◽  
Vitamin D Supplementation ◽  
Spectrum Disorder ◽  
Vitamin D Levels

: Autism spectrum disorder (ASD) is a pervasive developmental disorder with heterogeneous etiology. Vitamin D can function as a fat-soluble vitamin as well as a hormone, and can exert its effect through both genomic and non-genomic mechanisms. In the last decades, several studies have examined the relationship between vitamin D levels and ASD. These studies demonstrated that low vitamin D status in early development has been hypothesized as an environmental risk factor for ASD. Both in vivo and in vitro studies have demonstrated that vitamin D deficiency in early life can alter brain development, dysregulates neurotransmitter balance in the brain, decreases body and brain antioxidant ability, and alters the immune system in ways that resemble pathological features commonly seen in ASD. In this review, we focused on the association between vitamin D and ASD. In addition, the above-mentioned mechanisms of action that link vitamin D deficiency with ASD were also discussed. Finally, clinical trials of vitamin D supplementation treatment of ASD have also been discussed.

scholarly journals Autism Spectrum Disorder Risk Factor Met Regulates the Organization of Inhibitory Synapses

2021 ◽  
Vol 14 ◽  
Author(s):  
Pauline Jeckel ◽  
Martin Kriebel ◽  
Hansjürgen Volkmer
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Scaffolding Protein ◽  
Inhibitory Synapses ◽  
Gabaergic Synapses ◽  
The Impact

A common hypothesis explains autism spectrum disorder (ASD) as a neurodevelopmental disorder linked to excitatory/inhibitory (E/I) imbalance in neuronal network connectivity. Mutation of genes including Met and downstream signaling components, e.g., PTEN, Tsc2 and, Rheb are involved in the control of synapse formation and stabilization and were all considered as risk genes for ASD. While the impact of Met on glutamatergic synapses was widely appreciated, its contribution to the stability of inhibitory, GABAergic synapses is poorly understood. The stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin. Here, we show in vivo and in vitro that Met is necessary and sufficient for the stabilization of GABAergic synapses via induction of gephyrin clustering. Likewise, we provide evidence for Met-dependent gephyrin clustering via activation of mTOR. Our results support the notion that deficient GABAergic signaling represents a pathomechanism for ASD.

scholarly journals Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucia Janickova ◽  
Karin Farah Rechberger ◽  
Lucas Wey ◽  
Beat Schwaller
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Risk Gene

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder

2021 ◽  
Vol 11 (5) ◽  
pp. 556
Author(s):  
Madalina Andreea Robea ◽  
Alin Ciobica ◽  
Alexandrina-Stefania Curpan ◽  
Gabriel Plavan ◽  
Stefan Strungaru ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Social Behavior ◽  
Antiepileptic Drug ◽  
Alternative Model ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Zebrafish Model ◽  
Developmental Defects

Autism spectrum disorder (ASD) is one of the most salient developmental neurological diseases and remarkable similarities have been found between humans and model animals of ASD. A common method of inducing ASD in zebrafish is by administrating valproic acid (VPA), which is an antiepileptic drug that is strongly linked with developmental defects in children. In the present study we replicated and extended the findings of VPA on social behavior in zebrafish by adding several sleep observations. Juvenile zebrafish manifested hyperactivity and an increase in ASD-like social behaviors but, interestingly, only exhibited minimal alterations in sleep. Our study confirmed that VPA can generate specific ASD symptoms, indicating that the zebrafish is an alternative model in this field of research.

scholarly journals In Vivo Evidence of Reduced Integrity of the Gray–White Matter Boundary in Autism Spectrum Disorder

2017 ◽  
Author(s):  
Derek Sayre Andrews ◽  
Thomas A. Avino ◽  
Maria Gudbrandsen ◽  
Eileen Daly ◽  
Andre Marquand ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
White Matter ◽  
Autism Spectrum ◽  
Spectrum Disorder

Social performance–based interventions promote gains in social knowledge in the absence of explicit training for youth with autism spectrum disorder

2019 ◽  
Vol 83 (3) ◽  
pp. 301-325 ◽  
Author(s):  
Bianca M. Marro ◽  
Erin Kang ◽  
Kathryn M. Hauschild ◽  
Karys M. Normansell ◽  
Tamara M. Abu-Ramadan ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Engagement ◽  
Social Performance ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Knowledge ◽  
Community Based ◽  
Social Skills Interventions ◽  
Explicit Training

Youth with autism spectrum disorder (ASD) experience deficits in social knowledge. It has long been theorized that these youth must learn these skills explicitly, and social skills interventions (SSIs) have followed suit. Recently, performance-based SSIs have emerged, which promote in vivo opportunities for social engagement without explicit instruction. Effects of performance-based SSIs on social knowledge have not been examined. This study employs two discrete samples (one lab-based, one community-based) of youth with ASD to examine the effects of performance-based interventions on social knowledge. Results largely support the efficacy and effectiveness of improving social knowledge by performance-based interventions without explicit teaching. This indicates that youth with ASD may be able to learn these aspects of social cognition implicitly, rather than exclusively explicitly. The results of the current study also suggest that SSI content, dosage, and intensity may relate to these outcomes, which are important considerations in clinical practice and future studies.

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