In the first moments of human life, the brain is teeming with connections between neurons. As this intense brain development progresses, this activity decreases and sorting takes place in the synapses. It is this pruning process that scientists have just brought to light and which could help to understand certain cognitive disorders.
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When it is in full development, the brain must regularly sort through the countless connections formed by neurons who compose it. While we did not know how this sorting takes place, researchers have just identified a protein essential to this process: the A2A receiver. The latter could also be involved in cognitive disorders…
During brain development, there is an intense period during which neurons create many connections between them: this is the so-called period of synaptogenesis. The points of contact between neurons (or synapses “) multiply, then their quantity must be reduced so that the functioning of the brain is more efficient. We already knew that this phenomenon depended on neural activity — the synapses unused ones are eventually destroyed — but how this pruning process is controlled has until now been largely misunderstood.
To make progress on the subject, Christophe Bernard (unit 1106 Inserm/Aix-Marseille University, Institute of Systems Neuroscience, Physionet team, Marseille) and Sabine Lévi (unit 1270 Inserm/Sorbonne University, Institute of Iron at Moulin, team Plasticity cortical networks and epilepsy, Paris) looked at the case of GABAergic synapses. These connections, in which the molecule GABA serves as a chemical messenger, are particularly important: they are among the first to be formed and their activity is essential for the construction from the rest of neural circuit.
How are synapses sorted?
The work directed by the two researchers, conducted in mice, highlights light the key role of the A2A adenosine receptor in the sorting process: located at the synapse, this receptor allows the connection to be maintained when it is activated by adenosine (which then acts as a neurotransmitter ).
On the other hand, if it is not activated for more than 20 minutes, the elimination process begins. An experimental blockade of the receptor also leads to the destruction of the synapse. The A2A receiver would therefore act as a foreman in the arrangement of the central nervous system during development.
” One could compare the development of brain to a country under construction, in which each city is, at the start, connected to all the others by direct roads. The A2A receiver acts as an activity detector: as long as the road is taken by cars, the detector sends a fire red to the workers in charge of dismantling the roads. If no car passes for 20 minutes, it sends them a green light, and the road is removed “, explains Christophe Bernard.
In humans, the period of synaptogenesis probably takes place at the end of intrauterine life or in the very first times after birth, a phase during which the expression of A2A is known to be particularly strong.
A protein under the influence of caffeine
” It is now necessary to determine whether the synapses which function with other neurotransmitters, as the glutamate or theacetylcholine, are eliminated according to the same principle. Furthermore, it is known that A2A is activated by adenosine, but the mechanism that stimulates or inhibits the production of the latter depending on synaptic activity remains to be established. “, continues the researcher.
This fundamental work could have apps interesting clinics: We focused on the role of adenosine because we had previously observed that a high intake of caffeine during the period of synaptogenesis interferes with the natural functioning of the A2A protein. In animals, this results in subsequent cognitive impairment. We can therefore wonder if this phenomenon also exists in humans, especially since the production ofenzyme which degrades caffeine is reduced in pregnant women. »
The exhibition in utero to large amounts of caffeine cause cognitive impairment in the life of the unborn child? ” While we know its beneficial role for the cognitive functioning of adults, this hypothesis raises questions. We explore the question through a study funded by the National Research Agency and the Alzheimer Foundation. It aims to explain this effect, says “Janus”, which makes caffeine beneficial or harmful depending on age. »
It could, for example, be based on the triggering of different molecular mechanisms depending on the age at which the interaction takes place between caffeine and A2A. ” This study will undoubtedly allow us to better understand the mechanisms involved in the destruction or preservation of synapses. “, hopes Christophe Bernard. A work that could also provide important elements for the identification of new targets in the treatment of cognitive disorders or Alzheimer’s disease.
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