کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5735073 | 1612901 | 2017 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD](/preview/png/5735073.png)
چکیده انگلیسی
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms of social impairments and restrictive repetitive behaviors. Recent evidence has implicated a dysfunction in the GABAergic system in the pathophysiology of ASD. We investigated the role of endogenous allopregnanolone (ALLO), a neurosteroidal positive allosteric modulator of GABAA receptors, in the regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor of type I and type II 5α-reductase, a rate-limiting enzyme of ALLO biosynthesis. SKF impaired sociability-related performance, as analyzed by three different tests; i.e., the 3-chamber test and social interaction in the open field and resident-intruder tests, without affecting olfactory function elucidated by the buried food test. SKF also induced repetitive grooming behavior without affecting anxiety-like behavior. SKF had no effect on short-term spatial working memory or long-term fear memory, but enhanced latent learning ability in male mice. SKF-induced ASD-like behavior in male mice was abolished by the systemic administration of ALLO (1 mg/kg, i.p.) and methylphenidate (MPH: 2.5 mg/kg, i.p.), a dopamine transporter inhibitor. The effects of SKF on brain ALLO contents in male mice were reversed by ALLO, but not MPH. On the other hand, SKF failed to induce ASD-like behavior or a decline in brain ALLO contents in female mice. These results suggest that ALLO regulates episodes of ASD-like behavior by positively modulating the function of GABAA receptors linked to the dopaminergic system. Moreover, a sex-dependently induced decrease in brain ALLO contents may provide an animal model to study the main features of ASD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 334, 15 September 2017, Pages 6-15
Journal: Behavioural Brain Research - Volume 334, 15 September 2017, Pages 6-15
نویسندگان
Ken Ebihara, Hironori Fujiwara, Suresh Awale, Dya Fita Dibwe, Ryota Araki, Takeshi Yabe, Kinzo Matsumoto,