Investigating the Effect of Inosine on Brain Purinergic Receptors and Neurotrophic and Neuroinflammatory Parameters in an Experimental Model of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.

Inosine in Neurodegenerative Diseases: From the Bench to the Bedside

“…Furthermore, recently, Teixeira et al explored inosine action in the STZ-induced rat model of AD, focusing on the analysis of its effects on memory, neurotrophic factors, neuroinflammatory cytokines, purinergic receptor expression, and morphological changes in the rat hippocampus and cerebral cortex [ 33 ].…”

“…In particular, rats were distributed in four groups (control; STZ; STZ plus inosine at a dose of 50 mg/kg; and STZ plus inosine at a dose of 100 mg/kg) and were treated with intracerebroventricular injections of STZ or buffer [ 33 ]. Three days after the surgical procedure, they were treated with inosine (at a dose of 50 mg/kg or 100 mg/kg) for a period of 25 days [ 33 ].…”

“…Interestingly, inosine treatment prevented memory deficits, reduced the immunoreactivity of the brain A2A adenosine receptor induced by STZ, and enhanced the brain levels of anti-inflammatory cytokines as well as the expression of brain-derived neurotrophic factor and its receptor [ 33 ]. In addition, inosine was able to reduce the alterations induced by STZ in the molecular layer of the hippocampus and to protect against the decrease in immunoreactivity for synaptophysin induced by STZ in the CA3 hippocampal region [ 33 ]. On the other hand, inosine treatment was not able to prevent an increase in GFAP in rats treated with STZ [ 33 ].…”

“…In addition, inosine was able to reduce the alterations induced by STZ in the molecular layer of the hippocampus and to protect against the decrease in immunoreactivity for synaptophysin induced by STZ in the CA3 hippocampal region [ 33 ]. On the other hand, inosine treatment was not able to prevent an increase in GFAP in rats treated with STZ [ 33 ]. Overall, these data suggest that inosine could be a promising therapeutic strategy for AD due to its ability to modulate different brain mechanisms implicated in neuroprotection [ 33 ].…”

“…On the other hand, inosine treatment was not able to prevent an increase in GFAP in rats treated with STZ [ 33 ]. Overall, these data suggest that inosine could be a promising therapeutic strategy for AD due to its ability to modulate different brain mechanisms implicated in neuroprotection [ 33 ].…”