TY  - MANSCPT
AU  - Salem,Mohamed Ahmed Mahmoud
TI  - Possible modulatory effect of tadalafil and bergapten on experimentally induced cognitive impairment in mice
U1  - 615.19 22
PY  - 2021///
KW  - pharmacology
N1  - Supervision of Dr. Nesrine Salah El Dine El Sayed, Professor and Head of Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Dr. Suzan Mohamed Mansour, Associate Professor of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmacy, Future University in Egypt (FUE); Thesis (M.Sc.)-Cairo University, Faculty of Pharmacy, Department of Pharmacology & Toxicology, 2021; Includes bibliographical references
N2  - Sporadic Alzheimer’s disease (SAD) is a slowly progressive 
neurodegenerative disorder characterized by deposition of amyloid beta (Aβ) 
plaques, tau protein aggregation, impaired insulin signaling, and 
neuroinflammation. This study aimed to investigate the neuroprotective 
potential of tadalafil (TAD) and bergapten (BG) in SAD-induced cognitive 
impairment in mice. SAD was induced by a single intracerebroventricular 
injection of streptozotocin (STZ) (3 mg/kg). TAD or BG was administered 
intraperitoneally at doses of 20 and 25 mg/kg, respectively, 5 hours after STZ 
injection for 21 consecutive days. TAD and BG conceivably attenuated STZinduced hippocampal insult, preserved neuronal integrity, and improved 
cognitive function in the Morris water maze and object recognition tests 
paralleled by reduced Aβ expression and phosphorylation of tau. Moreover, 
TAD and BG enhanced the protein expression of pAkt, pGSK-3β, beclin-1, 
and methylated protein phosphatase 2A (PP2A) and cyclin D1 gene expression 
and raised brain-derived neurotrophic factor immunoreactivity. In addition, 
both drugs boosted the hippocampal levels of cyclic guanosine 
monophosphate (cGMP), protein kinase G (PKG), WNT3A, and adenosine 
monophosphate-activated protein kinase coupled by reduced protein 
expression of β-catenin and mammalian target of rapamycin (mTOR). TAD 
and BG also halted neuroinflammation as evidenced by reduced IL-23 and IL27 levels and NF-κB protein expression. However, the effects of BG were 
superior than that of TAD on the restoration of the brain histological profile.
In conclusion, this study offers novel insights on the neuroprotective effects 
of TAD or BG in the management of AD as evidenced by the improved 
cognitive function and histopathological architecture. This could be attributed 
to modulation of the crosstalk among Akt/GSK-3β, PP2A, mTOR/autophagy, 
cGMP/PKG, and Wnt/β-catenin signaling cascades and mitigation of 
neuroinflammation

UR  - http://repository.fue.edu.eg/handle/123456789/6045
ER  -