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The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels.
Mol Neurobiol. 2017 05; 54(4):2852-2868.MN

Abstract

Inhibition of Ca[2+] entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca[2+]-permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP). Thirty-two aged (18-24 months old) rats were divided into four groups. The first and second groups received a placebo and SCOP (1 mg/kg/day), respectively. The third and fourth groups received intraperitoneal Se (1.5 mg/kg/ over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We found that Se was fully effective in reversing SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working memory and reference memory. In addition, Se completely reduced SCOP-induced oxidative toxicity by modulating lipid peroxidation, reducing glutathione and glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP-ribose) polymerase activity, intracellular free Ca[2+] concentrations, apoptosis, and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the hippocampus. In conclusion, the current study reports on the cellular level for SCOP and Se on the different endocytotoxic cascades for the first time. Notably, the research indicates that Se can result in remarkable neuroprotective and memory impairment effects in the hippocampal neurons of rats. Graphical abstract Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP) induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus neurons of aged rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress, although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). The beta-amyloid plaque induces oxidative stress in hippocampus. SCOP can result in augmented ROS release in hippocampal neurons, leading to Ca[2+] uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca[2+] provided that intracellular Ca[2+] rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Se reduced TRPM2 and TRPV1 channel activation through the modulation of aging oxidative reactions and Se-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

Authors+Show Affiliations

Department of Psychiatry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.Department of Neuroscience, Institute of Health Science, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. Neuroscience Research Center, University of Suleyman Demirel, TR-32260, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr.Department of Psychiatry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.Department of Neuroscience, Institute of Health Science, Suleyman Demirel University, Isparta, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27021021

Citation

Balaban, Hasan, et al. "The Protective Role of Selenium On Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: the Involvement of TRPM2 and TRPV1 Channels." Molecular Neurobiology, vol. 54, no. 4, 2017, pp. 2852-2868.
Balaban H, Nazıroğlu M, Demirci K, et al. The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels. Mol Neurobiol. 2017;54(4):2852-2868.
Balaban, H., Nazıroğlu, M., Demirci, K., & Övey, İ. S. (2017). The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels. Molecular Neurobiology, 54(4), 2852-2868. https://doi.org/10.1007/s12035-016-9835-0
Balaban H, et al. The Protective Role of Selenium On Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: the Involvement of TRPM2 and TRPV1 Channels. Mol Neurobiol. 2017;54(4):2852-2868. PubMed PMID: 27021021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels. AU - Balaban,Hasan, AU - Nazıroğlu,Mustafa, AU - Demirci,Kadir, AU - Övey,İshak Suat, Y1 - 2016/03/28/ PY - 2016/02/12/received PY - 2016/03/04/accepted PY - 2016/3/30/pubmed PY - 2017/7/8/medline PY - 2016/3/30/entrez KW - Apoptosis KW - Dementia KW - Oxidative stress KW - Selenium KW - TRPM2 KW - TRPV1 SP - 2852 EP - 2868 JF - Molecular neurobiology JO - Mol Neurobiol VL - 54 IS - 4 N2 - Inhibition of Ca[2+] entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca[2+]-permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP). Thirty-two aged (18-24 months old) rats were divided into four groups. The first and second groups received a placebo and SCOP (1 mg/kg/day), respectively. The third and fourth groups received intraperitoneal Se (1.5 mg/kg/ over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We found that Se was fully effective in reversing SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working memory and reference memory. In addition, Se completely reduced SCOP-induced oxidative toxicity by modulating lipid peroxidation, reducing glutathione and glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP-ribose) polymerase activity, intracellular free Ca[2+] concentrations, apoptosis, and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the hippocampus. In conclusion, the current study reports on the cellular level for SCOP and Se on the different endocytotoxic cascades for the first time. Notably, the research indicates that Se can result in remarkable neuroprotective and memory impairment effects in the hippocampal neurons of rats. Graphical abstract Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP) induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus neurons of aged rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress, although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). The beta-amyloid plaque induces oxidative stress in hippocampus. SCOP can result in augmented ROS release in hippocampal neurons, leading to Ca[2+] uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca[2+] provided that intracellular Ca[2+] rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Se reduced TRPM2 and TRPV1 channel activation through the modulation of aging oxidative reactions and Se-dependent glutathione peroxidase (GSH-Px) antioxidant pathways. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/27021021/The_Protective_Role_of_Selenium_on_Scopolamine_Induced_Memory_Impairment_Oxidative_Stress_and_Apoptosis_in_Aged_Rats:_The_Involvement_of_TRPM2_and_TRPV1_Channels_ DB - PRIME DP - Unbound Medicine ER -