Congenital Malformations in a VPA-Induced Rat Model of Autism Spectrum Disorder

Abstract

Autism is a disorder with a spectrum of behavioral, developmental and neurological symptoms and has genetic and environmental etiology. Prenatal exposure to valproic acid (VPA) induces autism like symptoms in rodents and it is a favored model because of its similar aspects in humans. 8 pregnant Wistar albino rats were used in this study. 5 of them received 400 mg/kg/ml VPA and 3 of them received same volume of vehicle on E12,5. 79 offsprings (nVPA: 48, nctrl: 31) were grossly examined on P22. Among 48 of the VPA exposed pups, 30 of them showed physical malformations whereas there were no malformations observed in the control group. Displayed malformations are as follows; tail bends in 22 out of 48 (45,83%), extra digit-like paw malformations in 8 out of 48 (16,66%) and position deformity with motor strength loss in foot in 1 out of 48 (2,08%). Distribution of the malformations among sexes was insignificant. Bends in tails were characterized by location and severity. Proximal tail bends were more common than middle and distal locations. Our results support the teratogenic effects of in utero VPA exposure which were seen as physical malformations. Further studies are required to unreveal possible correlations of malformations with behavioral symptoms. Our findings enhance the facial validity of VPA induced models of autism and broaden model’s symptomatic spectrum.

Keywords

• Autism,Valproic Acid,Animal Model,Teratogen,Malformation

Valproik Asitle İndüklenmiş Otizm Spektrum Bozukluğu Sıçan Modelinde Doğumsal Malformasyonlar

Abstract

Otizm genetik ve çevresel bir etiolojiye sahip davranışsal, gelişimsel ve nörolojik semptomlarla görülen bir spektrum bozukluğudur. Prenatal dönemde valproik asit (VPA) maruziyeti sıçanlarda otizm benzeri semptomlara neden olur ve insanlarda da benzer etkiler göstermesi nedeniyle tercih edilen bir modeldir. Çalışmamızda 8 gebe Wistar albino sıçan kullanılmıştır. E12,5’de 5 anne sıçan 400 mg/kg/ml VPA’e, 3 anne sıçan ise aynı volümde serum fizyolojiğe maruz kalmıştır. Doğan 79 yavru (nVPA: 48, nctrl: 31) P22’de muayene edilmiştir. VPA’e maruz kalmış 48 yavrudan 30’u malformasyonlara sahipken, kontrol grubu yavrularda herhangi bir malformasyon görülmemiştir. Görülen malformasyonlar; 48 hayvanın 22’sinde (%45,83) kuyruk kırılması, 8’inde (%16,66) ekstra parmak benzeri pati deformasyonu, ve 1’inde (%2,08) ayak duruş deformitesi ve motor kuvvet kaybı şeklindedir. Cinsiyetler arasında malformasyon dağılımı bakımından bir fark yoktur. Kuyruk kırılmaları lokasyon ve ciddiyet bakımından karakterize edilmiştir. Kuyruğun proksimal kısmında orta ve distal kısma göre daha fazla kırılma görülmüştür. Sonuçlarımız fiziksel malformasyonlar şeklinde karşımıza çıkan VPA’in teratojenik etkilerini doğrular niteliktedir. Malformasyonlar ve davranışsal semptomlar arasındaki muhtemel ilişki için ek çalışmalar gerekmektedir. Bulgularımız VPA maruziyetiyle oluşturulan otizm modelinin semptomatik geçerliliğini artırmakta ve modelin semptomatik spektrumunu genişletmektedir. 

Keywords

• Otizm,Valproik Asit,Hayvan Modeli,Teratojen,Malformasyon

References

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