Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities

被引:7
作者
Teixeira, Fernanda Cardoso [1 ,4 ]
de Mattos, Bruna da Silveira [1 ]
de Mello, Julia Eisenhardt [1 ]
Cardoso, Juliane [1 ]
Spohr, Luiza [1 ]
Luduvico, Karina Pereira [1 ]
Soares, Mayara Sandrielly Pereira [1 ]
Carvalho, Fabiano Barbosa [2 ]
Gutierres, Jessie Martins [2 ]
Oliveira Campello Felix, Anelize de [3 ]
Stefanello, Francieli Moro [1 ]
Spanevello, Roselia Maria [1 ,4 ]
机构
[1] Univ Fed Pelotas, Programa Posgrad Bioquim & Bioprospeccao, Ctr Ciencias Quim Farmaceut & Alimentos, Campus Univ S-N, Pelotas, RS, Brazil
[2] Univ Fed Ciencias Saude Porto Alegre, Programa Posgrad Patol, Lab Pesquisa Patol, Porto Alegre, RS, Brazil
[3] Univ Fed Pelotas, Bioterio Cent, Pelotas, RS, Brazil
[4] Univ Fed Pelotas, Programa Posgrad Bioquim & Bioprospeccao, Lab Neuroquim Inflamacao & Canc, Ctr Ciencias Quim Farmaceut & Alimentos, Campus Univ, BR-96010900 Pelotas, RS, Brazil
关键词
Memory; Oxidative stress; Acetylcholinesterase activity; Na+; K+-ATPase activity; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; ACETYLCHOLINESTERASE; ATPASE; ANTHOCYANINS; ACQUISITION; ACTIVATION; BUTYRYLCHOLINESTERASE; HIPPOCAMPUS; DEMENTIA;
D O I
10.1007/s11064-021-03460-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.
引用
收藏
页码:446 / 460
页数:15
相关论文
共 54 条
[1]   Molecular mechanisms of memory acquisition, consolidation and retrieval [J].
Abel, T ;
Lattal, KM .
CURRENT OPINION IN NEUROBIOLOGY, 2001, 11 (02) :180-187
[2]  
AEBI H, 1984, METHOD ENZYMOL, V105, P121
[3]   Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer's disease [J].
Aksenov, MY ;
Markesbery, WR .
NEUROSCIENCE LETTERS, 2001, 302 (2-3) :141-145
[4]  
ALI SF, 1992, NEUROTOXICOLOGY, V13, P637
[5]   Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer's Disease [J].
Amato, Antonella ;
Terzo, Simona ;
Mule, Flavia .
ANTIOXIDANTS, 2019, 8 (12)
[6]   Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats [J].
Bernabeu, R ;
Bevilaqua, L ;
Ardenghi, P ;
Bromberg, E ;
Schmitz, P ;
Bianchin, M ;
Izquierdo, I ;
Medina, JH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (13) :7041-7046
[7]   Spermidine decreases Na+,K+-ATPase activity through NMDA receptor and protein kinase G activation in the hippocampus of rats [J].
Carvalho, Fabiano B. ;
Mello, Carlos F. ;
Marisco, Patricia C. ;
Tonello, Raquel ;
Girardi, Bruna A. ;
Ferreira, Juliano ;
Oliveira, Mauro S. ;
Rubin, Maribel A. .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2012, 684 (1-3) :79-86
[8]   PROTECTION BY INOSINE IN A CELLULAR MODEL OF PARKINSON'S DISEASE [J].
Cipriani, S. ;
Bakshi, R. ;
Schwarzschild, M. A. .
NEUROSCIENCE, 2014, 274 :242-249
[9]   Organosulfur compound protects against memory decline induced by scopolamine through modulation of oxidative stress and Na+/K+ ATPase activity in mice [J].
da Silva, Fernanda D. ;
Pinz, Mikaela P. ;
de Oliveira, Renata L. ;
Rodrigues, Karline C. ;
Ianiski, Francine R. ;
Bassaco, Mariana M. ;
Silveira, Claudio C. ;
Jesse, Cristiano R. ;
Roman, Silvane S. ;
Wilhelm, Ethel A. ;
Luchese, Cristiane .
METABOLIC BRAIN DISEASE, 2017, 32 (06) :1819-1828
[10]   Inosine improves functional recovery after experimental traumatic brain injury [J].
Dachir, Shlomit ;
Shabashov, Dalia ;
Trembovler, Victoria ;
Alexandrovich, Alexander G. ;
Benowitz, Larry I. ;
Shohami, Esther .
BRAIN RESEARCH, 2014, 1555 :78-88