000			03474cam a2200325 a 4500
003			EG-GiCUC
008			210414s2021 ua dh f m 000 0 eng d
040			_aEG-GiCUC _beng _cEG-GiCUC
041	0		_aeng
049			_aDeposite
097			_aM.Sc
099			_aCai01.08.09.M.Sc.2021.Sa.S
100	0		_aSamar Mamdouh Mohamed Shawki
245	1	2	_aA study of the possible curative effect of Liraglutide {u2013} a Glucagon-like Peptide -1 analog - on cognitive deficits in 3-Nitropropionic acid {u2013}Induced Huntington{u2019}s Disease in rats / _cSamar Mamdouh Mohamed Shawki ; Supervised Hanan S. Eabhar , Walaa Wadie Ibrahim , Rania Mohammed Rahmo
246	1	5	_aدراسة عن التأثير العلاجى المحتمل لنظير الببتيد الشبيه بالجلوكاجون -1:ليراجلوتايد فى نموذج مرض هنتنغتون المحدث تجريبيا بواسطة حمض3- النيتروبروبيونيك فى الجرذان
260			_aCairo : _bSamar Mamdouh Mohamed Shawki , _c2021
300			_a130 P . : _bcharts , facsmilies ; _c25cm
502			_aThesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
520			_aIntroduction: Huntington{u2019}s disease (HD) is a dominant autosomal neurodegenerative disease associated with progressive motor and cognitive deficits that lacks a definitive symptomatic therapy. The antidiabetic liraglutide possesses a neuroprotective potential against models of neurodegenerative disorders; however, its role in HD remains elusive which is the aim of this work. Methods: Liraglutide (200 og/kg, s.c) was administered to rats intoxicated with 3-nitropropionic acid (3-NP) for 4 weeks post HD model induction. Results: Liraglutide abated the 3-NP-induced neurobehavioral deficits tested by open field and elevated plus maze tests, effects that were mirrored on the improved histopathological findings. To further emphasize its neuroprotective role, liraglutide markedly downregulated the striatal mRNA expression of HSP 27, PBR and GFAP, while it upregulated that of DARPP32. On the molecular level, liraglutide enhanced striatal miR-130a gene expression and TrKB protein expression and its ligand BDNF, while reduced the striatal protein content and mRNA expression of the death receptors sortilin and p75NTR, respectively. Additionally, it enhanced the neuroprotective molecules cAMP, p-PI3K, p-Akt and p-CREB, besides modulating the p-GSK-3Ý/p-Ý-catenin axis. Liraglutide also proved its anti-oxidant/-apoptotic capacity that were verified by enhancing the antioxidant transcription factor Nrf2 and abrogating MDA, besides, upregulating both Bcl2 and Bcl-XL and downregulating Bax along with decreasing caspase-3 activity. Conclusion: based on these findings, liraglutide exerts a neuroprotective effect on 3-NP treated rats that is at least partially attributed to the increase of miR-130a and modulation of PI3K/Akt/CREB/BDNF/TrKB, sortilin and p75NTR, and Akt/ GSK-3Ý/p-Ý-catenin trajectories besides its anti-apoptotic, antioxidant, and neurotrophic activities
530			_aIssued also as CD
653		4	_a3-nitropropionic acid
653		4	_aBDNF/TrkB
653		4	_aHuntington{u2019}s disease
700	0		_aHanan S. Eabhar, _eSupervisor
700	0		_aRania Mohammed Rahmo , _eSupervisor
700	0		_aWalaa Wadie Ibrahim , _eSupervisor
905			_aAmira _eCataloger
905			_aNazla _eRevisor
942			_2ddc _cTH
999			_c80651 _d80651