New neurons are formed regularly in the adult brain to ensure that all
our cognitive capacities are maintained. This neurogenesis may be adversely
affected in various situations, especially:
- in the course of ageing,
- after radiotherapy treatment of a brain tumour. (The irradiation of certain
areas of the brain is, in fact, a central adjunctive therapy for brain tumours
in adults and children).
According to some studies, the reduction in our “stock” of neurons
contributes to an irreversible decline in cognition. In the mouse, for example,
researchers reported that exposing the brain to radiation of approximately 15 Gy
is accompanied by disruption to the olfactive memory and a reduction in
neurogenesis. The same happens in ageing, where a reduction in neurogenesis is
associated with a loss of certain cognitive faculties. The same phenomena can be
observed in patients receiving radiotherapy due to the removal of a brain
tumour.
Researchers are studying how to preserve the “neuron stock”. To do
this, they have tried to discover which factors are responsible for the decline
in neurogenesis. Contrary to what might have been expected, their initial
observations show that neither heavy doses of radiation nor ageing are
responsible for the complete disappearance of the neural stem cells capable of
producing neurons (and thus the origin of neurogenesis). Those that survive
remain localised in a certain small area of the brain (the sub-ventricular zone
(SVZ)). They nevertheless appear to be incapable of working correctly.Additional
experiments have established that in both situations, irradiation and ageing,
high levels of the cytokine TGFβ cause the stem cells to become dormant,
increasing their susceptibility to apoptosis (PCD) and reducing the number of
new neurons.
“Our study concluded that although neurogenesis reduced in ageing and after a
high dose of radiation, many stem cells survive for several months, retaining
their ‘stem’ characteristics”, explains Marc-Andre Mouthon, one of the main
authors of the research, which was conducted in conjunction with José Piñeda and
François Boussin. The second part of the project demonstrated that
pharmacological blocking of TGFβ restores the production of new neurons in
irradiated or ageing mice.For the researchers, these results will encourage the
development of targeted therapies to block TGFβ in order to reduce the impact of
brain lesions caused by radiotherapy and improve the production of neurons in
the elderly presenting with a cognitive decline.