Andrographolide Attenuates Short-Term Spatial and Recognition Memory Impairment and Neuroinflammation Induced by a Streptozotocin Rat Model of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder clinically manifested by a gradual cognitive decline. Intracerebroventricular injection (ICV) of streptozotocin (STZ), a model of sporadic AD (sAD), shows many aspects of sAD abnormalities (i.e., neuroinflammation, oxidative stress, protein aggregation), resulting in memory impairment. Andrographolide (ANDRO), a natural diterpene lactone, has numerous bioactivities including anti-inflammatory and antioxidant properties. Studies in rodents revealed that ANDRO has neuroprotective properties and restores cognitive impairment. In the present study, we investigated the effects of ANDRO in the ICV-STZ model relative to short-term spatial memory (object location test (OLT) and Y maze test), short-term recognition memory (object recognition test (ORT)), locomotor activity (open field test (OFT)), expression of amyloid precursor protein (APP), and activation of astrocytes (glial fibrillary acidic protein (GFAP) expression) and microglia (ionized calcium-binding adapter molecule-1 (Iba-1) immunohistochemistry) in the prefrontal cortex (PFC) and hippocampus (HIP). Wistar rats were injected ICV with STZ (3mg/kg) or vehicle and treated with ANDRO (2mg/kg, i.p.; three times per week). After four weeks, ANDRO attenuated the impairments of the Y maze and ORT performances, and the increase of astrocyte activation in the PFC induced by the ICV-STZ model. In addition, ANDRO decreased the number of activated microglia cells in the HIP of STZ-injected rats. The APP expression was not altered, neither by the STZ nor ANDRO. ANDRO showed a beneficial effect on memory impairment and neuroinflammation in the STZ model of AD.