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A cAMP analog attenuates beta-amyloid (1-42)-induced mitochondrial dysfunction and spatial learning and memory deficits.
Brain Res Bull. 2018 06; 140:34-42.BR

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.

Authors+Show Affiliations

Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@tums.ac.ir.Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: j.pourahmadjaktaji@utoronto.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29605485

Citation

Aghsami, Mehdi, et al. "A cAMP Analog Attenuates Beta-amyloid (1-42)-induced Mitochondrial Dysfunction and Spatial Learning and Memory Deficits." Brain Research Bulletin, vol. 140, 2018, pp. 34-42.
Aghsami M, Sharifzadeh M, Sepand MR, et al. A cAMP analog attenuates beta-amyloid (1-42)-induced mitochondrial dysfunction and spatial learning and memory deficits. Brain Res Bull. 2018;140:34-42.
Aghsami, M., Sharifzadeh, M., Sepand, M. R., Yazdankhah, M., Seyednejad, S. A., & Pourahmad, J. (2018). A cAMP analog attenuates beta-amyloid (1-42)-induced mitochondrial dysfunction and spatial learning and memory deficits. Brain Research Bulletin, 140, 34-42. https://doi.org/10.1016/j.brainresbull.2018.03.016
Aghsami M, et al. A cAMP Analog Attenuates Beta-amyloid (1-42)-induced Mitochondrial Dysfunction and Spatial Learning and Memory Deficits. Brain Res Bull. 2018;140:34-42. PubMed PMID: 29605485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A cAMP analog attenuates beta-amyloid (1-42)-induced mitochondrial dysfunction and spatial learning and memory deficits. AU - Aghsami,Mehdi, AU - Sharifzadeh,Mohammad, AU - Sepand,Mohammad Reza, AU - Yazdankhah,Meysam, AU - Seyednejad,Seyed Afshin, AU - Pourahmad,Jalal, Y1 - 2018/03/29/ PY - 2017/11/21/received PY - 2018/03/24/revised PY - 2018/03/26/accepted PY - 2018/4/2/pubmed PY - 2019/6/5/medline PY - 2018/4/2/entrez KW - Beta amyloid KW - Hippocampus KW - Mitochondrial function KW - Protein kinase A KW - Spatial memory SP - 34 EP - 42 JF - Brain research bulletin JO - Brain Res Bull VL - 140 N2 - 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. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/29605485/A_cAMP_analog_attenuates_beta_amyloid__1_42__induced_mitochondrial_dysfunction_and_spatial_learning_and_memory_deficits_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(17)30690-1 DB - PRIME DP - Unbound Medicine ER -