Leña

Así es, señoras y señores, ñiños y ñiñas, jóvenes y jóvenes, tengo el agrado de presentarles el lanzamiento mundial de mi nueva obra cómica-mágica-musical-científica. Les prometo meto y les repito pito que se le verá publicada en el futuro próximo en alguna de esas revistas con "ribiugüers". Otrora se le podrá devisar en el congreso de la sociedad para las neurociencias ahí pal año que viene.
Chicles!


Uncompetitive NMDA-R blockade prevents neurodegeneration induced by mitochondrial dysfunction in the mouse retina in vivo.

Background. Mitochondrial dysfunction and excitotoxicity are thought to be critical interrelated events involved in the pathogenesis of neurodegenerative diseases. By inducing oxidative stress and energy depletion, inhibition of the mitochondrial respiratory chain may contribute to NMDA receptor mediated excitotoxicity and cell death.

Aim. The aim of this study is to test the hypothesis that uncompetitive NMDA-R blockade with memantine prevents cell death in vivo, using a novel mouse model of retinal ganglion cell layer degeneration induced by rotenone, a specific mitochondrial complex I inhibitor.

Methods. Mice received intravitreal injections of rotenone, rotenone/memantine or vehicle. Apoptosis in the ganglion cell layer (GCL) was evaluated using the TUNEL technique and morphological retinal changes were estimated using stereological techniques.

Results. One hr post-injection, rotenone induced an increase in the number of apoptotic cells in GCL compared to controls (7.2 ± 2.8 vs. 3 ± 0.3 apoptotic cells per section, respectively, p < 0.05). Apoptosis was prevented by the co-administration of 70 m/kg memantine (0.5 ± 0.3 apoptotic cells per section). The neurotoxic effect of rotenone was also reflected as a decrease in total cell density in the GCL (26,792 ± 2885 cells/mm3 vs. control 33,476 ± 3694 cells/mm3) and GCL + nerve fiber layer thickness (16.3 ± 0.9 mm vs. control 24.2 ± 1.3 mm, p < 0.5), 24 hr after injection. These changes were also prevented by co-administration of memantine in a dose-dependent manner (cell density 40,427 ± 3972, 42,680 ± 3839 and 40,040 ± 6181 cells/mm3 and GCL + NFL thickness 16.9 ± 1.7, 18.9 ± 2.4, 21.8 ± 1.5 mm for memantine 0.7, 7 and 70 mg/kg, respectively, p < 0.05).

Conclusion. These results suggest that NMDA-R activation plays a role in apoptosis induced by mitochondrial dysfunction and that uncompetitive NMDA-R blockade may be used as a strategy to prevent cell loss in neurodegenerative disorders.