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

Yıl 2019, , 151 - 156, 01.08.2019

Süeda Tunçak , Bülent Gören Tayfun Uzbay Pınar Öz

https://doi.org/10.32708/uutfd.547540

Öz

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.

Anahtar Kelimeler

Autism, Valproic Acid, Animal Model, Teratogen, Malformation

Valproik Asitle İndüklenmiş Otizm Spektrum Bozukluğu Sıçan Modelinde Doğumsal Malformasyonlar

Öz

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. 

Anahtar Kelimeler

Otizm, Valproik Asit, Hayvan Modeli, Teratojen, Malformasyon

Kaynakça

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