MITOCHONDRIAL DYSFUNCTION IN DOWN’S SYNDROME NEURONS MAY REFLECT AN ADAPTIVE RESPONSE TO OXIDATIVE STRESS

HELGUERA P; BUSCIGLIO J

Mendoza

Congreso; NEUROTOXICITY SOCIETY 2011; 2011

<!-- /* Font Definitions */ @font-face {font-family:Cambria; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin-top:0in; margin-right:0in; margin-bottom:10.0pt; margin-left:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-ascii-font-family:Cambria; mso-fareast-font-family:Cambria; mso-hansi-font-family:Cambria; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:ES-TRAD;} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> SUMMARY  Down´s Syndrome (DS) or trisomy of chromosome 21 is the most common autosomal aneuploidy that survives birth.  DS individuals show a very high prevalence of chronic disorders including diabetes, Alzheimer’s disease and mental retardation.  Our previous work suggests that chronic mitochondrial dysfunction may lead to persistent systemic deficits on cell capability and viability.  Thus, mitochondrial dysfunction may be a critical element of DS pathology. Structural and functional alterations exist in mitochondria of several DS cell types including neurons, astrocytes and fibroblasts. DS neurons present functional and morphological changes in mitochondria, including loss of mitochondrial membrane potential, decreased ATP production, reduced oxidoreductase activity and increased fragmented mitochondrial morphology.  Comparative studies between NL and DS cells indicated a differential pattern of secretory activity. Interestingly, these functional alterations in DS cells were partially rescued by a treatment that combined trolox (antioxidant) and creatine (energy buffer). However, under these conditions, DS cells generated higher levels of superoxide radicals and lipid peroxidation.