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 (3 mg/kg) or vehicle and treated with ANDRO (2 mg/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.
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Acknowledgements
We thank Professor Marcelo M.S. Lima (Department of Physiology, Federal University of Parana) for allowing us to conduct part of the experiments in the facilities of the Laboratory of Neurophysiology and Professor Silvio M. Zanata (Department of Basic Pathology, Federal University of Parana) for the support.
Funding
This work was supported by grants from Coordination for the Improvement of Higher Education Personnel (CAPES) and Araucaria Foundation to Support Scientific and Technological Development of the State of Paraná (No. 88882.168580/2018–01), which had no further role in the study design, collection, analysis, and interpretation of the data, writing the report, and decision to submit the paper for publication. MABFV is a recipient of a National Council for Scientific and Technological Development (CNPq) fellowship (No. 309567/2019–0).
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Leonardo C. Souza contributed to the conceptualization, methodology, validation, formal analysis, investigation, data curation, writing—original draft, writing—review and editing, and visualization. Marcos K. Andrade and Evellyn M. Azevedo were involved in the formal analysis, investigation, and data curation.. Daniele C. Ramos contributed to the investigation and writing—review and editing. Ellen L. Bail contributed to the investigation. Maria A. B. F. Vital helped in the conceptualization, methodology, resources, writing—review and editing, visualization, supervision, project administration, and funding acquisition.
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Souza, L.C., Andrade, M.K., Azevedo, E.M. et al. Andrographolide Attenuates Short-Term Spatial and Recognition Memory Impairment and Neuroinflammation Induced by a Streptozotocin Rat Model of Alzheimer’s Disease. Neurotox Res 40, 1440–1454 (2022). https://doi.org/10.1007/s12640-022-00569-5
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DOI: https://doi.org/10.1007/s12640-022-00569-5