REDUCTION OF beta-AMYLOID-INDUCED NEUROTOXICITY ON HIPPOCAMPAL CELL CULTURES BY MODERATE ACIDOSIS IS MEDIATED BY TRANSFORMING GROWTH FACTOR beta

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dc.contributor.authorMartin, R. Uribe San
dc.contributor.authorHerrera Molina, R.
dc.contributor.authorOlavarria, L.
dc.contributor.authorRamirez, G.
dc.contributor.authorvon Bernhardi, R.
dc.date.accessioned2024-01-10T13:17:09Z
dc.date.available2024-01-10T13:17:09Z
dc.date.issued2009
dc.description.abstractProgression of Alzheimer's disease (AD) is associated with chronic inflammation and microvascular alterations, which can induce impairment of brain perfusion because of vascular pathology and local acidosis. Acidosis can promote amyloidogenesis, which could further contribute to neurodegenerative changes. Nevertheless, there is also evidence that acidosis has neuroprotective effects in hypoxia models. Here we studied the effect of moderate acidosis on beta-amyloid (A beta)-mediated neurotoxicity. We evaluated morphological changes, cell death, nitrite production and reductive metabolism of hippocampal cultures from Sprague-Dawley rats exposed to A beta under physiological (pH 7.4) or moderate acidosis (pH 7.15-7.05). In addition, because transforming growth factor beta (TGF beta) 1 is neuroprotective and is induced by several pathophysiological conditions, we assessed its presence at the different pHs. The exposure of hippocampal cells to A beta induced a conspicuous reduction of neurites' arborization, as well as increased neuronal death and nitric oxide production. However, A beta neurotoxicity was significantly attenuated when hippocampal cultures were kept at pH 7.15-7.05, showing a 68% reduction on lactate dehydrogenase release compared with cultures exposed to A beta at pH 7.4 (P<0.01). Similarly, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction increased 3.5-fold (P<0.05), and A beta-induced nitrite production was reduced by 65% when exposed to moderate acidosis compared with basal pH media (P<0.05). At the same time, moderate acidosis decreased intracellular TGF beta 1 precursor (latency associated protein-TGF beta 1) and increased up to fourfold TGF beta 1 bioactivity, detecting a 43% increase in the active TGF beta levels in cultures exposed to A beta and moderate acidosis. Inhibition of TGF beta signaling abolished the neuroprotective effect of moderate acidosis. Our results show that moderate acidosis protected hippocampal cells from A beta-mediated neurotoxicity through the increased activation and signaling potentiation of TGF beta. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
dc.description.funderFONDECYT
dc.description.funderVRAID of the Pontificia Universidad Catolica de Chile
dc.fechaingreso.objetodigital03-04-2024
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.neuroscience.2008.11.002
dc.identifier.eissn1873-7544
dc.identifier.issn0306-4522
dc.identifier.pubmedidMEDLINE:19041694
dc.identifier.urihttps://doi.org/10.1016/j.neuroscience.2008.11.002
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78641
dc.identifier.wosidWOS:000263775800015
dc.information.autorucBachillerato;Uribe San Martin R.;S/I;127201
dc.information.autorucMedicina;Von Bernhardi R;S/I;62523
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1347
dc.pagina.inicio1338
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.revistaNEUROSCIENCE
dc.rightsacceso restringido
dc.subjectAlzheimer's disease
dc.subjectbeta-amyloid
dc.subjectcell death
dc.subjectneurodegeneration
dc.subjectneuroinflammation
dc.subjecttransforming growth factor beta 1
dc.subjectFOCAL CEREBRAL-ISCHEMIA
dc.subjectIN-VITRO ISCHEMIA
dc.subjectALZHEIMERS-DISEASE
dc.subjectNMDA RECEPTOR
dc.subjectGLUTAMATE NEUROTOXICITY
dc.subjectMICROGLIAL REACTIVITY
dc.subjectPRECURSOR PROTEIN
dc.subjectBRAIN-TISSUE
dc.subjectNITRIC-OXIDE
dc.subjectACTIVATION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleREDUCTION OF beta-AMYLOID-INDUCED NEUROTOXICITY ON HIPPOCAMPAL CELL CULTURES BY MODERATE ACIDOSIS IS MEDIATED BY TRANSFORMING GROWTH FACTOR beta
dc.typeartículo
dc.volumen158
sipa.codpersvinculados127201
sipa.codpersvinculados62523
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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