Neuroprotective effect of Tropisetron in Streptozotocin induced animal model of Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease is a neurodegenerative pathology having genetic and non‐genetic forms. Non‐genetic forms of AD dominate over the genetic condition and is mainly sporadic. However, both forms affect cognitive functions. Although exact mechanisms are not fully understood, amyloid β deposition & tau tangle formation are considered central mechanisms to cause neurodegenerative changes in the AD brain. On the other hand, cognitive deterioration began way before the accumulation of amyloid or tau tangle formation. Cognitive functions, including learning and memory, have been majorly controlled/regulated by the cholinergic system. Here in the present study, we have explored the neuroprotective effect of tropisetron in streptozotocin‐induced animal model of Alzheimer’s disease. During the last two decades, the involvement of other neurotransmitter systems has been explored, and the serotonergic system has been demonstrated to play an essential role in memory and learning. The serotonergic system is the most extensive monoaminergic system in the brain, and alterations in serotonergic signals have been linked with Aβ and tau tangle formation. Moreover, serotonin acting through its receptor antagonist has been reported beneficial in various experimental AD models.MethodIn the present study animals were infused with STZ alternatively on 1st and 3rd day. From 15th day animals were treated with tropisteron with two subsequent doses (2.2.5mg/kg) and (5mg/kg). On 28th day animals were sacrificed. Further animals were tested for behavioral, biochemical and histopathological parameters.ResultTropisetron significantly attenuated oxidative damage and restored the reduced levels of anti‐oxidant enzymes. ICV‐STZ treatment had shown significant neuronal damage in hippocampal and cortical regions of AD brain in histopathological examination. Moreover, hippocampal neurons were observed to be irregular in morphology with dark pyknotic nuclei. This confirms the neurodegeneration in ICV‐STZ animals. Target drug tropisetron resulted in significant neuroprotection against ICV‐STZ.ConclusionThe observed outcomes of the present study suggest the neuroprotective effect of tropisteron in STZ induced animal model of Alzheimer’s disease.It would be safe to conclude that tropisetron may improve the behavioral outcomes by attenuating oxidative burden & its neuroprotective potential as seen in our histological assessment.