title: Memory-enhancing effect of aspirin is mediated through opioid system modulation in an AlCl3-induced neurotoxicity mouse model.
abstract: Neurodegenerative disorders such as Alzheimers disease (AD) are multifaceted and there are currently a limited number of therapeutic strategies available to treat them. Aspirin is known to act on multiple therapeutic targets and is a successful anti-inflammatory agent in various tissues. The present study aimed to ascertain the performance of aspirin when employed as a therapeutic agent to treat neurodegeneration on novel targets, including opioid system genes, in an AlCl3-induced neurotoxicity mouse model. The effects of two doses of aspirin (5 and 20 mg/kg aspirin for 12 days) were investigated in an AlCl3-induced neurotoxicity mouse model (150 mg/kg AlCl3for 12 days). Neurological improvements were assessed through different behavioral tests and the effects of aspirin on opioid system gene expression levels were assessed by reverse transcription-polymerase chain reaction. Both doses resulted in improvements in cognitive behavior. A 5 mg/kg dose of aspirin was revealed to be effective for spatial memory improvement (7.14±0.84 sec), whilst a 20 mg/kg dose was superior for improving extinction learning (7.63±4.04%). Aspirin (5 mg/kg) also significantly improved contextual memory (48.05±10.6%) when compared with the AlCl3-treated group (1.49±0.62%; P<0.001). Aspirin was also observed to significantly decrease δ-opioid receptor expression in the cortex (1.09±0.08 and 1.27±0.08, respectively) at both doses (5 and 20 mg/kg) when compared with the AlCl3-treated group (3.69±1.43; P<0.05). Furthermore, aspirin at 5 mg/kg significantly reduced expression of prodynorphin in the cortex (0.57±0.20) when compared with the AlCl3-treated group (1.95±0.84; P<0.05). Notably, the effect of aspirin was significant in the cortex but not in the hippocampus. In summary, aspirin was effective in ameliorating the AD-like symptoms via the modulation of opioid systems. However, additional studies are required to determine the long term effects of aspirin on such conditions.
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Rizwan
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, Pakistan.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Idrees
authors.affiliation: Department of Plant Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, Pakistan.
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
keywords: amygdala; fear memory; hippocampus; social preference; δ opioid receptors; κ opioid receptors