Abstract
Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD. Interestingly, it has been shown that increased S100B levels affect zinc homeostasis in vitro. Thus, here, we investigated the influence of increased S100B levels in vitro and in vivo during pregnancy in mice regarding zinc availability, the zinc-sensitive SHANK protein networks associated with ASD, and behavioral outcomes. We observed that S100B affects the synaptic SHANK2 and SHANK3 levels in a zinc-dependent manner, especially early in neuronal development. Animals exposed to high S100B levels in utero similarly show reduced levels of free zinc and SHANK2 in the brain. On the behavioral level, these mice display hyperactivity, increased stereotypic and abnormal social behaviors, and cognitive impairment. Pro-inflammatory factors and zinc-signaling alterations converge on the synaptic level revealing a common pathomechanism that may mechanistically explain a large share of ASD cases.
Highlights
Autism Spectrum Disorders (ASD) are a group of neurological disorders considered to manifest from a synaptic dysfunction or synaptopathy [1]
Immunocytochemistry performed on contrast to previous results, our data showed that early exposure to hippocampal neurons shows that after increasing S100B levels, S100B significantly affected both SHANK2 and SHANK3 levels (Fig. 2a, S100B added to the cell culture medium co-localizes with a b)
We wanted to analyze whether the decrease in intracellular given the effects of S100B on forming synapses, to zinc levels leads to destabilization of SHANK2 and SHANK3 investigate whether the observed alterations in zinc homeostasis complexes at the post-synaptic density (PSD) of excitatory synapses as previously reported and SHANK scaffold formation in vitro occur during brain
Summary
Autism Spectrum Disorders (ASD) are a group of neurological disorders considered to manifest from a synaptic dysfunction or synaptopathy [1]. We hypothesize that hypozincemia induced by increased different approaches and, the decrease of SHANK2 levels of S100B during brain development will affect synapse protein levels in crude membrane fractions 24 h after exposure to function and maturation, possibly via the autism-associated S100B was demonstrated by Western blot (WB) analysis (Fig. 1f). We synaptic SHANK2 signal intensity and affected SHANK3 levels investigated the impact of altered S100B protein levels on synapse significantly in this experiment. Zinc-saturated S100B formation and proteins of the SHANK family in vitro and in vivo did not significantly alter SHANK2 and SHANK3 signal intensities at and assessed the influence of prenatal exposure to elevated S100B synapses (Fig. 1g).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
