Effect of dimethyl fumarate on cognitive deficitsin experimentally-induced Alzheimer's disease /
تأثير ثنائى ميثيل فيوماريت على أختلالات التعرف الناتج عن مرض الزهايمر المحدث تجريبيا
Israa Mohamed Abdelfatah Ismail Farag ; Supervised Dalaal Moustafa Abdallah , Hanan Salah Eldin Elabhar , Heba Mohamed Ahmed Ali Abdelrazek
- Cairo : Israa Mohamed Abdelfatah Ismail Farag , 2021
- 129 P. : charts , facsimiles ; 25cm
Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
Since the role of estrogen in postmenauposal-associated dementia is still debatable, this issue urges the search for other medications. Dimethyl fumarate (DMF) is a drug used for the treatment of multiple sclerosis and has shown a neuroprotective effect against other neurodegenerative diseases. Accordingly, the present study aimed to evaluate the effect of DMF on an experimental model of Alzheimer disease (AD) using D-galactose (D-Gal) administered to ovariectomized (OVX) rats, resembling a postmenopausal dementia paradigm. Adult 18-month old female Wistar rats were allocated into sham-operated and OVX/D-Gal groups that were either left untreated or treated with DMF for 56 days starting three weeks after sham-operation or ovariectomy. DMF succeeded to ameliorate cognitive (learning/short- and long-term memory) deficits and to enhance the dampened overall activity (NOR, Barnes-/Y-maze tests).These behavioral upturns were associated with increased intact neurons (Nissl stain) and a reduction in OVX/D-Gal-mediated hippocampal CA1 neurodegeneration and astrocyte activation assessed as GFAP immunoreactivity. Mechanistically, DMF suppressed the hippocampal contents of AD-surrogate markers; viz., apolipoprotein (APO)-E1, BACE1, AÝ42, and hyperphosphorylated Tau. Additionally, DMF has augmented the neuroprotective parameters p-AKT, its downstream target CREB and BDNF. Besides, it activated AMPK, and enhanced SIRT-1, as well as antioxidant defenses (SOD, GSH)