Neurotrophic factor neuritin ameliorates streptozotocin-induced Alzheimer's disease-like impairment of memory, neuroinflammation, apoptotic factors and compensates hippocampal neuritin expression

Abstract

Alzheimer’s disease (AD) is the main cause of dementia in the elderly, and is becoming one of the most expensive and deadly diseases. Deficiency of neurotrophic factors signaling is an important cause of this disease. Therefore, we investigated whether neuritin as a neurotrophic factor can have a neuroprotective effect against streptozotocin (STZ)-induced rat model of AD. The animals were bilaterally injected with intra hippocampal-STZ (3 mg/kg). Different concentrations of neuritin (0.5, 1, 1.5 µg/rat) were administrated 15 min before STZ injection. After 14 days, the rats were evaluated for cognitive performance using novel object recognition (NOR), open field and Morris water maze (MWM) tests and then sacrificed for biochemical analysis (by real-time PCR and western blot examinations). The results demonstrated that the STZ- induced learning and memory impairments were significantly prevented by 1.5 µg neuritin. Moreover, the increased levels of inflammatory factors (NF-κb, TNF-α and IL-1β) and apoptotic parameters (cytochrome c and caspase‑3) in STZ- treated rats were also significantly decreased by neuritin. In addition, hippocampal neuritin gene expression was downregulated by STZ injection, which was reversed by intra hippocampal neuritin injection. In conclusion, the present study suggests that neuritin prevents cognitive defects in AD rat model and its expression level is associated with cognitive resilience.