In this study by Verret et al., the effect of overproduction of β amyloid on the genesis of new neurons in dentate gyrus of the hippocampus was studied in transgenic mice with Alzheimer-type amyloid pathology. This issue had been addressed in recent years in a number of studies with differing outcomes, showing either increased or decreased cell proliferation in the dentate gyrus. This is probably due in part because of the use of different transgenic lines and varying paradigms of administration of the marker for dividing cells, bromodeoxyuridine (BrdU).
The authors of the present study report that Alzheimer pathology does not affect the proliferation or production of new cells but does impair their ultimate survival and differentiation into new neurons. In this elegant study, three different transgenic lines are bred into the same parental background strains and compared directly to each other, preventing a possible confound of the effects of strain differences on cell genesis. In addition, the researchers used multiple low-dose injections of BrdU, which is a method with relatively slight variance and appropriate to assess short-term as well as long-term survival of newborn neurons. Indeed, it takes about 4 weeks for a newborn cell to become a full-fledged neuron, and this paper shows clearly that the deficit is at the end of this period when the cells undergo their final differentiation step. The relatively late appearance of a detrimental effect on neurogenesis also suggests that there is a window of time that could be used to rescue new neurons. Specifically, enriched environment, exercise, and pharmacological measures may be effective in this regard.
Overall this is a very nice paper, although it would have been of interest to test learning behavior in these transgenic mice to determine whether the line that shows the least neurogenesis (APP/PS1 mice) also has the poorest performance in spatial memory tasks.
Comments
In this study by Verret et al., the effect of overproduction of β amyloid on the genesis of new neurons in dentate gyrus of the hippocampus was studied in transgenic mice with Alzheimer-type amyloid pathology. This issue had been addressed in recent years in a number of studies with differing outcomes, showing either increased or decreased cell proliferation in the dentate gyrus. This is probably due in part because of the use of different transgenic lines and varying paradigms of administration of the marker for dividing cells, bromodeoxyuridine (BrdU).
The authors of the present study report that Alzheimer pathology does not affect the proliferation or production of new cells but does impair their ultimate survival and differentiation into new neurons. In this elegant study, three different transgenic lines are bred into the same parental background strains and compared directly to each other, preventing a possible confound of the effects of strain differences on cell genesis. In addition, the researchers used multiple low-dose injections of BrdU, which is a method with relatively slight variance and appropriate to assess short-term as well as long-term survival of newborn neurons. Indeed, it takes about 4 weeks for a newborn cell to become a full-fledged neuron, and this paper shows clearly that the deficit is at the end of this period when the cells undergo their final differentiation step. The relatively late appearance of a detrimental effect on neurogenesis also suggests that there is a window of time that could be used to rescue new neurons. Specifically, enriched environment, exercise, and pharmacological measures may be effective in this regard.
Overall this is a very nice paper, although it would have been of interest to test learning behavior in these transgenic mice to determine whether the line that shows the least neurogenesis (APP/PS1 mice) also has the poorest performance in spatial memory tasks.
Make a Comment
To make a comment you must login or register.