Estudo sobre o efeito neuroprotetor de cafeína em modelo animal de doença de Alzheimer induzida por estreptozotocina

Abstract

Alzheimer’s Disease is a syndrome of neuropathological neurodegenerative disruptions of a chronic and progressive nature, characterized by the development of senile plaques (or amiloid plaques), neurofibrillary tangles, dystrophic neurites and neuropil strands, associated with cognitive and behavioral deficits. The Streptozotocin model constitutes an effective tool for the investigation of the disease, and is based upon Intracerebroventricular injections of the drug Streptozotocin, which results in the reduction of the Insulin uptake via the desensitization of insulin receptors and IGFs, together with other effects, inducing the molecular, pathological and behavioral characteristics similar to those of Alzheimer’s Disease. The aim of this study was the investigation of the possible neuroprotective effects of Caffeine over this experimental model, measuring its effects on glycemia; locomotor activity; working memory, recognition memory, and short- and long-term aversive memories. To that end, 40 Swiss Specific Pathogen Free mice were equally divided into four groups, wherein the groups 1 and 2 received Intracerebroventricular injection with Artificial Cerebrospinal Fluid, and the groups 3 and 4 received Streptozotocin (3mg/Kg). The groups 1 and 2 were subsequently treated orally with Vehicle (potable water), and the groups 2 and 4 with caffeine (15 mg/Kg), also orally. Glycemia dosage was performed in every animal one day before the surgeries and the euthanasia, so as to confirm that they were not diabetic. There was no evidence of alterations in the glucose levels before or after the Intracerebroventricular Streptozotocin injection or the caffeine treatment. The animals did not demonstrate locomotor deficiencies. There was no indication of a significant alteration in their working memory. The animals that underwent Streptozotocin injection presented a lower recognition index, however the treatment with caffeine promoted a significant improvement. The animals subjected to Streptozotocin displayed long-term memory deficits, however those treated with Caffeine were protected from such a decline in the short- and long-term memories. The different groups did not display significant alterations in regards to anxiety and anxious behaviors. In such a way, Caffeine is capable of protecting mice from memory deficits induced by the Intracerebroventricular administration of Streptozotocin, suggesting it to have a neuroprotective role against cognitive losses and being capable, therefore, of serving as a possible neuroprotective and/or adjuvant strategy against Alzheimer’s Disease.