000 03341cam a2200325 a 4500
003 EG-GiCUC
008 170322s2016 ua dh f m 000 0 eng d
040 _aEG-GiCUC
_beng
_cEG-GiCUC
041 0 _aeng
049 _aDeposite
097 _aPh.D
099 _aCai01.08.09.Ph.D.2016.Lo.E
100 0 _aLobna Hatem Abdelghaphour Khedr
245 1 0 _aEffects of fluoxetine and pentoxifylline on stress-induced changes in the molecular paradigm of mitochondrial regulation in the hippocampus of male wistar rats /
_cLobna Hatem Abdelghaphour Khedr ; Supervised Ezzeddin Said Eldenshary , Ahmed M. Abdeltawab , Laila Rashed
246 1 5 _aتأثيرات الفلوكستين و البنتوكسيفلين في تغيرات محدثة بالكرب في نموذج جزيئي لنظام الميتوكوندريا في قرن آمون لذكور جرذان " ويستر
260 _aCairo :
_bLobna Hatem Abdelghaphour Khedr ,
_c2016
300 _a214 P. :
_bcharts , facsimiles ;
_c25cm
502 _aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
520 _aPrevious reports in our lab linked chronic mild stress (CMS), a well-validated model of depression, to impaired hippocampal energy metabolism and mitochondrial dysfunction. Adding repeated lipopolysaccharide (LPS) to CMS was recently proposed as another model of depression. The combined LPS/CMS model highlighted the possible interaction between stress and immune-inflammatory pathways and their impact on disrupting tryptophan metabolism and triggering TNF-Ü induced changes in the hippocampus along with depressive-like behavioral alterations. In the current study, the interplay between mitochondrial biogenesis and toll-like receptor 4 (TLR4) signaling, as a target for LPS, was investigated in a combined LPS/ CMS model. To this end, male Wistar rats were exposed to either LPS (50 og/kg i.p) over 2 weeks, CMS protocol for 4 weeks or LPS over 2 weeks followed by 4 weeks of CMS (LPS/CMS). Another three groups of rats were exposed to LPS/CMS protocol and treated with either pentoxifylline (PTX), fluoxetine (FLX) or a combination of both. Rats were examined for behavioral, neurochemical, gene expression and mitochondrial ultra-structural changes.Animals exposed to LPS/CMS showed perturbation of serum corticosterone (CORT) and {u2018}TNF-Ü{u2019} levels as well as behavioral responses. Interestingly, LPS/CMS attenuated the increased expression of TLR4 and its downstream players; MyD88 adaptor protein, nuclear factor kappa B (NFmB) and hippocampal TNF-Ü, compared to SAL/CMS. Moreover, LPS/CMS abridged the SAL/CMS effects on mitochondrial biogenesis machinery; peroxisome proliferator-activated receptor gamma co-activators1-alpha (PGC1-Ü). Furthermore, the antidepressant (AD) {u2018}FLX{u2019}, the TNF-Ü inhibitor {u2018}PTX{u2019} and their combination engendered a further enhancement in all the aforementioned LPS/CMS-induced changes (figure 1)
530 _aIssued also as CD
653 4 _aCMS
653 4 _aLPS
653 4 _aTLR-4 signaling
700 0 _aAhmed Moheyeldin Abdeltawab ,
_eSupervisor
700 0 _aEzzeddin Said Eldenshary ,
_eSupervisor
700 0 _aLaila Rashed ,
_eSupervisor
905 _aEnas
_eCataloger
905 _aNazla
_eRevisor
942 _2ddc
_cTH
999 _c59653
_d59653