دورية أكاديمية
S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
| العنوان: | S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis |
|---|---|
| المؤلفون: | Daini E., Hagmeyer S., De Benedictis C. A., Cristovao J. S., Bodria M., Ross A. M., Raab A., Boeckers T. M., Feldmann J., Gomes C. M., Zoli M., Vilella A., Grabrucker A. M. |
| المساهمون: | Daini, E., Hagmeyer, S., De Benedictis, C. A., Cristovao, J. S., Bodria, M., Ross, A. M., Raab, A., Boeckers, T. M., Feldmann, J., Gomes, C. M., Zoli, M., Vilella, A., Grabrucker, A. M. |
| سنة النشر: | 2021 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| مصطلحات موضوعية: | Animal, Brain, Female, Genetic Predisposition to Disease, Homeostasi, Mice, Microfilament Protein, Nerve Tissue Protein, Pregnancy, S100 Calcium Binding Protein beta Subunit, Autism Spectrum Disorder, Zinc |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34741005; info:eu-repo/semantics/altIdentifier/wos/WOS:000731670100001; volume:11; issue:1; firstpage:562; lastpage:562; journal:TRANSLATIONAL PSYCHIATRY; http://hdl.handle.net/11380/1275375Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85118559396 |
| DOI: | 10.1038/s41398-021-01694-z |
| الإتاحة: | https://doi.org/10.1038/s41398-021-01694-zTest http://hdl.handle.net/11380/1275375Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6464B220 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41398-021-01694-z |
|---|