Stem cells reproduce a new controversy?

Click the blue word to focus on whether adult neural regeneration in our mammals has been debated for decades
.

Experiments in non-human primates and rodents have demonstrated the existence of adult neurogenesis in the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus, of which reduced adult neurogenesis in the hippocampus has been implicated in the occurrence of depression and cognitive function in Alzheimer's disease mechanism of decline
.

In 1998, BrdU labeling technology was used to discover the existence of adult neural regeneration in the human hippocampus for the first time.
In 2003, the radioisotope carbon-14 technology was used to confirm this conclusion again.
Then in 2013, researchers further quantified that human hippocampal neurons were renewed at a rate of 1.
75% per year.
, by analyzing the number of neural progenitor cells can indirectly reflect the degree of neurogenesis, but does not provide information on whether these neural progenitor cells differentiate into immature neurons
.

When a cell undergoes mitosis and replicates its chromosomes, it integrates the isotope carbon-14 into the newly formed genomic DNA, further assessing the presence of neural regeneration by measuring the concentration of the isotope carbon-14 in genomic DNA at different times
.

On April 20, 2022, Hagen B.
Huttner's research team at the University of Erlangen-Nuremberg, Germany, found that there is nerve regeneration in the adult amygdala region by radioisotope labeling in the journal Communications biology
.

Figure 1: Absence of lipofuscin in some neurons of the adult amygdala Aggregating lipofuscin, a pigment that accumulates with age, has been shown to be absent from lipofuscin-positive neurons in 5-year-old human cortical tissue, Lipofuscin-positive neurons appear in adulthood
.

The researchers found severe lipofuscin accumulation in more than 90% of neurons in the amygdala region by post-mortem tissue from healthy adults (50-86 years old), but there were still 3.
4% of neurons with almost no lipofuscin expression (Fig.
1), indicating that these neurons are younger
.

They found differences in the concentrations of the isotope carbon-14 in the DNA of neurons in the amygdala region of these adults compared to the levels of the isotope carbon-14 in the atmosphere at birth, suggesting neural regeneration
.

To further assess the rate at which these neurons regenerate, they built three mathematical models, one of which assumed neurons to be updated at a fixed rate, calculated to average 0.
2% based on the concentration of the isotope carbon-14 in the DNA described above, with Regression fitting of this rate finally found that with increasing age, the average annual neural update rate was -0.
03%
.

Another model with a 1% rate of neuron update has a 75% chance that the rate of neuron update decreases with age
.

Reality is only met when updates are made at a minimum rate of 2.
7% per year
.

Tissue fixation methods, storage conditions and other external conditions will affect the immunohistochemical labeling of immature neurons (DCX or BrdU)
.

Furthermore, DCX is not only present in immature neurons, but also in mature neurons undergoing mitosis in the piriform cortex
.

Therefore, these endogenous factors or external factors will affect the error of immunolabeling, resulting in false positive or false negative results
.

In this paper, we found that there is nerve regeneration in the adult amygdala region by isotope technology, which once again pushed the controversy of nerve regeneration to a new height
.

[References] 1.
https://doi.
org/10.
1038/s42003-022-03299-8 The pictures in the text are from references