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003 | EG-GiCUC | ||
008 | 170322s2016 ua dh f m 000 0 eng d | ||
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_aEG-GiCUC _beng _cEG-GiCUC |
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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 |
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_aCairo : _bLobna Hatem Abdelghaphour Khedr , _c2016 |
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_a214 P. : _bcharts , facsimiles ; _c25cm |
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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 |
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700 | 0 |
_aEzzeddin Said Eldenshary , _eSupervisor |
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700 | 0 |
_aLaila Rashed , _eSupervisor |
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_aEnas _eCataloger |
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905 |
_aNazla _eRevisor |
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942 |
_2ddc _cTH |
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_c59653 _d59653 |