Young neurons in mature brains

Young neurons in mature brains

3150 2100 Peter Stevenson, PhD

A new study uncovered the existence of immature neurons in adult brains well into old age, adding more weight to the longstanding debate of whether neurogenesis really stops after adolescence.

The findings, published online in Nature Medicine1, were based on samples from 13 deceased adults aged 43–87. The researchers used fluorescent tags targeting doublecortin (DCX) protein – a gold-standard marker of immature neurons which can be readily assessed using a fluorescent microscope. Imaging revealed tens of thousands of DCX-positive cells in the dentate gyrus (tissue within the hippocampus that encodes memories of events).

The results also threw up some additional data on specific neurological progression. A 30% decrease in the number of immature neurons was identified between the youngest and oldest donor. Furthermore, Alzheimer’s disease was associated with 30% fewer immature neurons compared to samples of non-affected persons of the same age.

Identification of this seemingly fresh population of neurons in later life stands in contrast to a number of other previous studies which suggested that neurogenesis halts after adolescence2. However, a key difference in this new research was a much shorter time from sample creation to imaging (all within 24 hours, and most within 10), rather than months or even years in some previous studies, which could have had profound implications for results.2

Crucially, paraformaldehyde – a chemical fixation agent used to preserve tissue samples – is known to interfere with structure of DCX, making it more difficult for fluorescent tags to bind. The fluorescent signal is expected to decline sharply after 48 hours; thus, it has been postulated that negative results in these previous studies may be attributable to a diminished fluorescent signal rather than an actual lack of immature neurons.

But despite this compelling evidence for neurogenesis in later life, many remain sceptical. Criticisms of the study include non-specificity of the DCX fluorescent stain (mature cells also express the protein), and a lack of apparent stem-cell pools that would be needed to supply these fresh neurons.2

In defence, however, the researchers maintain that they backed up the DCX findings with other protein markers associated with neuronal development, several hallmarks of cellular youth, and maintained very strict protocols for confirming immature neurons.

As the authors conclude, “These results demonstrate the persistence of adult hippocampal neurogenesis during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in Alzheimer’s disease that might be amenable to novel therapeutic strategies.”


Sources

  1. Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, Rábano A, Cafini F, Pallas-Bazarra N et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nature Medicine. 2019.
  2. Underwood E. New neurons for life? Old people can still make fresh brain cells, study finds. Science Magazine.
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