Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by synaptic loss and cognitive impairments. Although AD is the most prevalent aging-related neurodegenerative disease, therapeutic strategies remain palliative. Recent studies have shown that probucol presents neuroprotective effects in experimental models of neurodegenerative disease. The present study aimed to investigate the potential protective effects of probucol against streptozotocin (STZ)-induced cognitive impairment and hippocampal biochemical changes (oxidative stress-related parameters, acetylcholinesterase (AChE) activity, cholesterol levels and β-secretase (BACE) protein levels) in mice. Adult Swiss mice received STZ [150μg/bilateral, i.c.v.], and treated daily with probucol (≅10mg/kg/day, in drinking water, for 5weeks,). Twenty-one days after i.c.v. administrations, STZ-infused animals displayed significant deficits in cognition (evaluated in the displaced and new object recognition tasks), which were paralleled by a significant increase in hippocampal AChE activity. Moreover, STZ-infused mice showed increased levels of BACE and decreased glutathione reductase (GR) activity in the hippocampus compared with the control group. Probucol treatment significantly protected against the behavioral and hippocampal biochemical changes induced by STZ. However, it was unable to prevent STZ-induced increase of hippocampal BACE levels and did not change hippocampal cholesterol levels. It is noteworthy that probucol treatment increased the glutathione peroxidase (GPx) activity per se independent of STZ injection. The present findings are the first to show that i.c.v. STZ infusions are able to increase hippocampal BACE expression. Moreover, the results also show that probucol can counteract STZ-induced cognitive impairments and biochemical parameters independently of potential modulator effects toward BACE levels. The study is the first to report the protective effects of probucol against STZ-induced biochemical hippocampal changes and behavioral impairments, rendering this compound a promising molecule for further pharmacological studies on the search for therapeutic strategies to treat or prevent AD.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
