Developmental exposure to the Fox River PCB mixture modulates behavior in juvenile mice

Basit Öğe Kaydı
dc.authorscopusidİlknur Dursun / 15126492700
dc.authorwosidİlknur Dursun / AGW-2134-2022
dc.contributor.authorWilson, Rebecca J.
dc.contributor.authorSuh, Youjun P.
dc.contributor.authorDursun, İlknur
dc.contributor.authorLi, Xueshu
dc.contributor.authorSouza, Felipe da Costa
dc.contributor.authorGrodzki, Ana Cristina
dc.contributor.authorCui, Julia Y.
dc.contributor.authorLehmler, Hans-Joachim
dc.date.accessioned2025-04-18T09:03:51Z
dc.date.available2025-04-18T09:03:51Z
dc.date.issued2024
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü
dc.description.abstractDevelopmental exposures to PCBs are implicated in the etiology of neurodevelopmental disorders (NDDs). This observation is concerning given the continued presence of PCBs in the human environment and the increasing incidence of NDDs. Previous studies reported that developmental exposure to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found in Aroclors caused NDD-relevant behavioral phenotypes in animal models. However, the PCB congener profile in contemporary human samples is dissimilar to that of the legacy Aroclors, raising the question of whether human-relevant PCB mixtures similarly interfere with normal brain development. To address this question, we assessed the developmental neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic the congener profile identified in fish from the PCB-contaminated Fox River that constitute a primary protein source in the diet of surrounding communities. Adult female C57BL/6 J mouse dams (8-10 weeks old) were exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in their diet throughout gestation and lactation, and neurodevelopmental outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and measures of general development were quantified at postnatal day (P) 7, while performance in the spontaneous alternation task and the 3-chambered social approach/social novelty task was assessed on P35. Triiodothyronine (T3) and thyroxine (T4) were quantified in serum collected from the dams when pups were weaned and from pups on P28 and P35. Developmental exposure to FRM did not alter pup weight or body temperature on P7, but USVs were significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in the maternal diet. FRM also impaired male and female pups' performance in the social novelty task. Compared to sex-matched vehicles, significantly decreased social novelty was observed in male and female pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance in the spontaneous alternation or social approach tasks. FRM increased serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0 and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered. Collectively, these findings suggest that FRM interferes with the development of social communication and social novelty, but not memory, supporting the hypothesis that contemporary PCB exposures pose a risk to the developing brain. FRM had sex, age, and dose-dependent effects on serum thyroid hormone levels that overlapped but did not perfectly align with the FRM effects on behavioral outcomes. These observations suggest that changes in thyroid hormone levels are not likely the major factor underlying the behavioral deficits observed in FRM-exposed animals.
dc.identifier.citationWilson, R. J., Suh, Y. P., Dursun, I., Li, X., da Costa Souza, F., Grodzki, A. C., ... & Lein, P. J. (2024). Developmental exposure to the Fox River PCB mixture modulates behavior in juvenile mice. Neurotoxicology, 103, 146-161.
dc.identifier.doiI10.1016/j.neuro.2024.06.008
dc.identifier.endpage161
dc.identifier.issn0161-813X
dc.identifier.issn1872-9711
dc.identifier.pmid38885884
dc.identifier.scopus2-s2.0-85196378189
dc.identifier.scopusqualityQ2
dc.identifier.startpage146
dc.identifier.urihttp://dx.doi.org/10.1016/j.neuro.2024.06.008
dc.identifier.urihttps://hdl.handle.net/20.500.12713/6680
dc.identifier.volume103
dc.identifier.wosWOS:001275740700001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorDursun, İlknur
dc.institutionauthoridİlknur Dursun / 0000-0001-7094-3336
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofNeuroToxicology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakTUBITAK 2219-1059B192000996
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBehavioral Assessment
dc.subjectCommunication
dc.subjectDevelopmental Neurotoxicity
dc.subjectPolychlorinated Biphenyls
dc.subjectSocial Behavior
dc.subjectThyroid Hormones
dc.titleDevelopmental exposure to the Fox River PCB mixture modulates behavior in juvenile mice
dc.typeArticle

Dosyalar

Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.17 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Temel Tıp Bilimleri Bölümü Makale Koleksiyonu