Fernanda Cardoso Teixeira1, Jessié Martins Gutierres2, Mayara Sandrielly Pereira Soares1, Bruna da Siveira de Mattos1, Luiza Spohr1, Carlus Augustu Tavares do Couto1, Natália Pontes Bona1, Charles Elias Assmann3, Vera Maria Morsch3, Ivana Beatrice Mânica da Cruz4, Francieli Moro Stefanello1, Roselia Maria Spanevello5,6. 1. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil. 2. Programa de Pós-Graduação em Patologia, Laboratório de Pesquisa em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil. 3. Programa de Pós-Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. 4. Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. 5. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil. rspanevello@gmail.com. 6. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário, Capão do Leão, Pelotas, RS, 96010-900, Brazil. rspanevello@gmail.com.
Abstract
RATIONALE: Inosine is a naturally occurring purine nucleoside formed by adenosine breakdown. This nucleoside is reported to exert potent effects on memory and learning, possibly through its antioxidant and anti-inflammatory actions. OBJECTIVE: The objective is to evaluate the effects of inosine on the behavioral and neurochemical parameters in a rat model of Alzheimer's disease (AD) induced by streptozotocin (STZ). METHODS: Adult male rats were divided into four groups: control (saline), STZ, STZ plus inosine (50 mg/kg), and STZ plus inosine (100 mg/kg). STZ (3 mg/kg) was administered by bilateral intracerebroventricular injection. The animals were treated intraperitoneally with inosine for 25 days. Memory, oxidative stress, ion pump activities, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities and expression were evaluated in the cerebral cortex and hippocampus. RESULTS: The memory impairment induced by STZ was prevented by inosine. An increase in the Na+, K+-ATPase, and Mg-ATPase activities and a decrease in the Ca2+-ATPase activity were induced by STZ in the hippocampus and cerebral cortex, and inosine could prevent these alterations in ion pump activities. Inosine also prevented the increase in AChE activity and the alterations in AChE and ChAT expression induced by STZ. STZ increased the reactive oxygen species, nitrite levels, and superoxide dismutase activity and decreased the catalase and glutathione peroxidase activities. Inosine treatment conferred protection from these oxidative alterations in the brain. CONCLUSIONS: Our findings demonstrate that inosine affects brain multiple targets suggesting that this molecule may have therapeutic potential against cognitive deficit and tissue damage in AD.
RATIONALE: Inosine is a naturally occurring purine nucleoside formed by adenosine breakdown. This nucleoside is reported to exert potent effects on memory and learning, possibly through its antioxidant and anti-inflammatory actions. OBJECTIVE: The objective is to evaluate the effects of inosine on the behavioral and neurochemical parameters in a rat model of Alzheimer's disease (AD) induced by streptozotocin (STZ). METHODS: Adult male rats were divided into four groups: control (saline), STZ, STZ plus inosine (50 mg/kg), and STZ plus inosine (100 mg/kg). STZ (3 mg/kg) was administered by bilateral intracerebroventricular injection. The animals were treated intraperitoneally with inosine for 25 days. Memory, oxidative stress, ion pump activities, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities and expression were evaluated in the cerebral cortex and hippocampus. RESULTS: The memory impairment induced by STZ was prevented by inosine. An increase in the Na+, K+-ATPase, and Mg-ATPase activities and a decrease in the Ca2+-ATPase activity were induced by STZ in the hippocampus and cerebral cortex, and inosine could prevent these alterations in ion pump activities. Inosine also prevented the increase in AChE activity and the alterations in AChE and ChAT expression induced by STZ. STZ increased the reactive oxygen species, nitrite levels, and superoxide dismutase activity and decreased the catalase and glutathione peroxidase activities. Inosine treatment conferred protection from these oxidative alterations in the brain. CONCLUSIONS: Our findings demonstrate that inosine affects brain multiple targets suggesting that this molecule may have therapeutic potential against cognitive deficit and tissue damage in AD.
Authors: N V Gulyaeva; N V Bobkova; N G Kolosova; A N Samokhin; M Yu Stepanichev; N A Stefanova Journal: Biochemistry (Mosc) Date: 2017-10 Impact factor: 2.487
Authors: V Ibáñez; P Pietrini; G E Alexander; M L Furey; D Teichberg; J C Rajapakse; S I Rapoport; M B Schapiro; B Horwitz Journal: Neurology Date: 1998-06 Impact factor: 9.910
Authors: Daniel Schuch da Silva; Mayara Sandrielly Pereira Soares; Fernanda Cardoso Teixeira; Júlia Eisenhardt de Mello; Anita Avila de Souza; Karina Pereira Luduvico; Cinthia Melazzo de Andrade; Roselia Maria Spanevello; Wilson Cunico Journal: Neurochem Res Date: 2021-03-23 Impact factor: 3.996
Authors: Alex B Speers; Manuel García-Jaramillo; Alicia Feryn; Donald G Matthews; Talia Lichtenberg; Maya Caruso; Kirsten M Wright; Joseph F Quinn; Jan F Stevens; Claudia S Maier; Amala Soumyanath; Nora E Gray Journal: Front Pharmacol Date: 2021-12-16 Impact factor: 5.810