Age‐associated alterations of lipofuscin, membrane‐bound ATPases and intracellular calcium in cortex, striatum and hippocampus of rat brain: protective role of glutathione monoester

Abstract

Brain aging has become an area of intense research and a subject of much speculation fueled largely from the widely recognized fact that age is the biggest risk factor in most neurodegenerative diseases and age-related increase of reactive oxygen species is particularly detrimental to postmitotic tissues. In the present study, we have evaluated the possible role of glutathione monoester (GME), when administered intraperitoneally (12mg/kg body weight) for 20 days on age-associated changes in the levels of lipofuscin, Na+K+, Mg2+, Ca2+ ATPase activities and intracellular calcium levels in discrete brain regions of young and aged male albino Wistar rats. An age-associated increase in lipofuscin, intracellular calcium in cortex, striatum and hippocampus was observed and contradictorily, a decrease in the activities of membrane-bound enzyme activities was also observed. Supplementation of GME brought these changes to near normalcy. Thus, GME improves neuronal antioxidant status, thereby effectively attenuating any putative increase in oxidative stress with age.

A switch in the mode of the sodium/calcium exchanger underlies an age-related increase in the slow afterhyperpolarization

“…There is also evidence that Na + /K + ATPase alpha-2 isoform knockout mice have increased [Ca 2+ ] stores (Lynch, et al, 2008). Furthermore, a reduction in the activity of this pump has been observed in central neurons of rats during aging (Benzi, et al, 1994, Murali, et al, 2008,Torlinska and Grochowalska, 2004. It is possible that the [Na + ]i in old CGCs may be elevated to such an extent that the driving force for Na + entry is reversed, causing Ca 2+ to be transported into the cell.…”

Analysis of data integrity

“…This important safety feature would pre- Figure 1. Illustrative results for (a) a paper from one of three investigators [6] (showing 60 of 60 CVs within the 50% limits; p = 8.7 · 10 )19 ) and (b) a representative control paper [7] (showing 36 of 112 CVs within the 50% limits; p > 0.99). The CVs are plotted on the y-axis for each mean and SD (or SE), which are consecutively numbered, on the x-axis.…”

“…Only one of these 29 papers demonstrated 'unusual clustering', which to our surprise turned out to be a paper from the same institution as the three investigators, but from a different department. Figure 1(a) shows CVs for all means and SDs from a paper of one of the investigators [6], and Fig. 1(b) A response to a previously published article or letter must be submitted via the dedicated correspondence website at www.anaesthesiacorrespondence.com, following the guidance there and using the online form (not uploaded as a Word attachment).…”

Calcium overload is associated with lipofuscin formation in human retinal pigment epithelial cells fed with photoreceptor outer segments

“…13,14 A recent study has suggested that lipofuscin deposition is significantly reduced via preventing the dysregulation of intracellular Ca 2 þ and this benefits the rat's brain. 15 The retina is closely related to the brain and they share a lot of similarities. However, the relationship between Ca 2 þ and lipofuscin in the retina is poorly understood.…”