Protective Effects of Antioxidant Pretreatment in VPA-Treated Nrf2 Knockout Mice
Başlık:
Protective Effects of Antioxidant Pretreatment in VPA-Treated Nrf2 Knockout Mice
Yazar:
Gifford, Janace J., author.
ISBN:
9780438106901
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (53 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Özet:
Genetic and environmental factors associated with oxidative stress have been implicated in the etiology of autism. The present study attempted to mimic the factors in an animal model of autism. Specifically, mice with a deletion of the Nrf2 gene, a master regulator for downstream enzymes associated with management of toxicant-generated reactive oxygen species, were administered valproic acid (VPA), a toxicant known to engender oxidative stress and one that has been associated with autism in humans. Prior studies revealed that VPA treatment induces functional and pathological changes in mice akin to autism. Further, previous work has established that pretreatment with antioxidants has the ability to protect mice from these VPA-induced functional deficits. The present study extended these observations to mice with alterations in NRF2 expression. On postnatal day 14 knockout (KO) and wild type (WT) mice were exposed to VPA (400 mg/kg) or saline and pretreated with either Trolox, a water-soluble form of vitamin E, or saline 1 hour prior to VPA. The behavioral tasks employed assessed maturation of normal social, cognitive, and motor skills and classified toxicant-induced deficits along a developmental timeline. Treatment with VPA resulted in deficits in mid-air righting and Morris water maze learning. Further, Trolox pretreatment prior to VPA provided partial protection from deficits associated with VPA treatment and this protective effect was more apparent in the Nrf2 KO mice. The results of the present study, at least in part, indicate the importance of Nrf2 during development as it might relate to autism and, more generally, the effects of oxidative stress during early development as well as the potential protective effects of antioxidant pretreatment.
Notlar:
School code: 0190
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(696433.1) | 696433-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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