000			02745na a2200229 4500
003			H12O
005			20210625062752.0
008			130622s2011 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_aGarcía Bueno, Borja _91897 _eInstituto de Investigación i+12
245	0	0	_aOrigin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression _h[artículo]
260			_bJournal of Neuroinflammation, _c2011
300			_a8:151.
500			_aFormato Vancouver: Gárate I, García Bueno B, Madrigal JL, Bravo L, Berrocoso E, Caso JR, et al. Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression. J Neuroinflammation. 2011;8:151.
501			_aPMID: 22053929
504			_aContiene 62 referencias
520			_aThere is a pressing need to identify novel pathophysiological pathways relevant to depression that can help to reveal targets for the development of new medications. Toll-like receptor 4 (TLR-4) has a regulatory role in the brain's response to stress. Psychological stress may compromise the intestinal barrier, and increased gastrointestinal permeability with translocation of lipopolysaccharide (LPS) from Gram-negative bacteria may play a role in the pathophysiology of major depression. Methods: Adult male Sprague-Dawley rats were subjected to chronic mild stress (CMS) or CMS+intestinal antibiotic decontamination (CMS+ATB) protocols. Levels of components of the TLR-4 signaling pathway, of LPS and of different inflammatory, oxidative/nitrosative and anti-inflammatory mediators were measured by RT-PCR, western blot and/or ELISA in brain prefrontal cortex. Behavioral despair was studied using Porsolt's test. Results: CMS increased levels of TLR-4 and its co-receptor MD-2 in brain as well as LPS and LPS-binding protein in plasma. In addition, CMS also increased interleukin (IL)-1 beta, COX-2, PGE(2) and lipid peroxidation levels and reduced levels of the anti-inflammatory prostaglandin 15d-PGJ(2) in brain tissue. Intestinal decontamination reduced brain levels of the pro-inflammatory parameters and increased 15d-PGJ2, however this did not affect depressive-like behavior induced by CMS. Conclusions: Our results suggest that LPS from bacterial translocation is responsible, at least in part, for the TLR-4 activation found in brain after CMS, which leads to release of inflammatory mediators in the CNS. The use of Gram-negative antibiotics offers a potential therapeutic approach for the adjuvant treatment of depression.
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc115.pdf _ySolicitar documento
942			_n0 _2ddc _cART
999			_c115 _d115