Volume 8, Issue 3 (Vol.8 No.3 Oct 2019)                   rbmb.net 2019, 8(3): 287-300 | Back to browse issues page

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Mostafa Tork O, Ahmed Rashed L, Bakr Sadek N, Abdel-Tawab M S. Targeting Altered Mitochondrial Biogenesis in the Brain of Diabetic Rats: Potential Effect of Pioglitazone and Exendin-4. rbmb.net. 2019; 8 (3) :287-300
URL: http://rbmb.net/article-1-359-en.html
Medical Biochemistry, Faculty of Medicine, Beni-Suef University.
Abstract:   (289 Views)
Background:Neuroprotective mechanisms triggered by peroxisome proliferator-activated receptor-gamma agonist: pioglitazone (PIO) and glucagon-like peptide 1 analog: exendin-4 (Ex-4) in neurological diseases were reported, but whether mitochondrial biogenesis is involved or not in their neuro-protective mechanisms in type 1 Diabetes Mellitus (T1DM); has not been studied before. To bridge this gap, we investigated the effect of PIO and Ex-4 on brain mitochondrial biogenesis in streptozotocin-induced diabetes in rats.
Methods:Seven weeks after induction of diabetes in rats, serum fasting glucose and insulin were measured in studied groups. The brain was removed for histological analysis and assessment of: mitochondrial complexes I and II, ATP, H2O2, brain derived neurotrophic factor (BDNF), cytochrome c and hemeoxygenase (HO)-1 activity, and relative gene expression of the nuclear factor; Nrf2and the apoptotic markers: bax& bcl2and mitochondrial biogenesis markers; peroxisome proliferator–activated receptor γ coactivator (PGC) 1-α and sirtuin 1 (SIRT-1) and AMP-activated protein kinase (AMPK) and c-Jun-N-terminal kinase (JNK) proteins.
Results:Brain in untreated rats showed neurodegeneration area and significantly rising H2O2and JNK, up-regulation of bax, down-regulation of bcl2. These changes were paralleled with significant reduction in Nrf2, HO-1, BDNF, complex I, II and ATP and SIRT-1/ PGC1-αexpression. PIO and Ex-4 significantly improved the reported changes. Combined modality showed better improvement relative to each drug alone.
Conclusions:PIO and Ex-4 may have neuroprotective effects in T1DM, via targeting altered mitochondrial biogenesis probably due to modulation of brain SIRT-1signaling, improvement of oxidative stress and equilibrating the balance between pro-apoptotic and anti-apoptotic mediators.
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Type of Article: Original Article | Subject: Biochemistry
Received: 2019/05/22 | Accepted: 2019/06/3 | Published: 2020/01/24

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