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  • Title: A cAMP analog attenuates beta-amyloid (1-42)-induced mitochondrial dysfunction and spatial learning and memory deficits.
    Author: Aghsami M, Sharifzadeh M, Sepand MR, Yazdankhah M, Seyednejad SA, Pourahmad J.
    Journal: Brain Res Bull; 2018 Jun; 140():34-42. PubMed ID: 29605485.
    Abstract:
    Alzheimer's disease (AD), a neurodegenerative disorder in elderly, is indicated with deposition of Amyloid β (Aβ) in the brain and accompanied with cognitive impairment. Bucladesine, a phosphodiesterase inhibitor, may ameliorate AD's cognitive dysfunctions through mimicking the action of cAMP and raising its intracellular level. Here, we investigated the effects of bucladesine on Aβ-induced memory and learning impairment in a Morris water maze (MWM) model. Rats were injected with bucladesine (1 μl/side from a 100 μM stock solution) and Aβ (1 μl/side from a 100 μM stock solution) intra-hippocampally and after 19 days were trained for 4 successive days. The oxidative stress was evaluated through measurement of thiobarbituric acid (TBARS), thiol groups, and ferric reducing antioxidant power (FRAP). Effect of Aβ and its combination with bucladesine on the mitochondrial function was assessed according to changes in the ROS generation, mitochondrial membrane potential (MMP), mitochondrial swelling, ATP/ADP ratio, mitochondrial outer membrane damage and cytochrome C release. Our results showed a significant elevation in TBARS level after administration of Aβ causing mitochondrial ROS generation, swelling, outer membrane damage, cytochrome C release and also lower thiol, FRAP, and MMP levels. Aβ-induced spatial memory impairment was prevented by pre-treatment with bucladesine and the changed mitochondrial and biochemical indices upon treatment dose were improved. Taken together, we have obtained satisfactory results suggesting protecting effects of bucladesine against the Aβ-mediated memory deficit and implying its plausible beneficial capacity as a therapeutic agent in oxidative stress-associated neurodegenerative diseases.
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