Eylem Seç
The Integrated Role of Wnt Signaling, mTOR Signaling and Glutamate Metabolism as a Possible Drug Target for Epilepsy in HBP1-/- Mice
Başlık:
The Integrated Role of Wnt Signaling, mTOR Signaling and Glutamate Metabolism as a Possible Drug Target for Epilepsy in HBP1-/- Mice
Yazar:
AlKhelb, Dalal A., author.
ISBN:
9780438031142
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (37 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Amy Yee Committee members: Eric Paulson.
Özet:
We have shown that Wnt signaling is activated in the hippocampus 5 days following status epilepticus (SE), and that Wnt signaling activates a Warburg-like metabolic program. We hypothesized that Wnt-signaling induced Warburg metabolism contributes to the ratio of GABA to glutamate, which is a critical factor in the progression to chronic seizures and whose syntheses derive from TCA cycle intermediates. To probe the role of Wnt signaling, we used HBP1 knockout mice (HBP1-/-). HBP1 is a Wnt signaling inhibitor; is expressed in hippocampal CA1-CA3; and may have human genetic association with seizures. Specifically, HBP1-/- mice should have elevated Wnt signaling, and provide a means of analyzing the proposed model. Our biochemical analysis shows that HBP1-/- mice have high Wnt signaling; decreased AMPK phosphorylation; and high mTOR signaling in hippocampal extracts. HBP1-/- mice have spontaneous seizures and have elevated sensitivity to pilocarpine induction of SE. Furthermore, glutamine synthase and glutaminase expression were significantly changed, as well as the expression of glutamate transporter; EAAT3 neuronal transporter and GLT-1 astrocytic transporter. Coupled with these changes were a marked increase in gliosis, suggesting that astrocyte expansion and metabolism may play a role in the pathogenesis of seizures in HBP1 knockout model.
Notlar:
School code: 0845
Konu Başlığı:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(688979.1) | 688979-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.