2023-12-12 15:44:13
Researchers have discovered the role of a brain regulator involved in certain psychological disabilities (schizophrenia) and neurodevelopmental disorders (autism), making it possible to consider new therapeutic avenues. Electrical study!
New major advance in the understanding of neurodevelopmental disorders (TND) and certain psychiatric illnesses? The complexity of the functioning of the brain reveals many surprises… Against all expectations, the receptor supposedly “exciter” called GluD1 would play a major role in controlling the inhibition of neurons. While this gene is often associated with autism, bipolar disorders or even schizophrenia in genetic studies, the precise understanding of its role constitutes a major challenge and might open the way to new therapeutic avenues. This discovery is the fruit of the work of researchers, from the National Institute of Health and Medical Research (Inserm) in particular*, published in the American scientific journal Science.
The role of a neuron
To fully understand this complex challenge, a quick reminder of the fundamentals. A neuron is a nerve cell capable of receiving, analyzing and producing information. It generates and propagates this ” action potential “ along its axon (nerve fiber), then transmits this signal through a synapse (point of contact between two neurons or between a neuron and a cell) by releasing neurotransmitters. These allow neurons to communicate with each other. Those that release neurotransmitters are called “presynaptic neurons” and those that receive them “postsynaptic neurons.” Synapses can be of two natures: excitatory or inhibitory.
Excitatory and inhibitory synapses
An excitatory synapse triggers the creation of a nerve message, in the form of an electrical current, if a receptor on its surface can attach to an excitatory neurotransmitter, most often glutamate. Conversely, an inhibitory synapse prevents prolonged activation of neurons by releasing an inhibitory neurotransmitter, often GABA. Thus, the family of glutamate receptors (iGluR) and that of GABA receptors (GABAAR) a priori have opposite roles. This was without counting on GluD1, a glutamate receptor subtype, which plays spoilsport… “While it is supposed to have an excitatory role, it is preferentially found at the level of inhibitory synapses”, observe the researchers. To see more clearly, the team of Pierre Paoletti, Inserm research director, studied its molecular properties and its function using mouse brains.
GluD1 strengthens the inhibitory signal
The researchers were also surprised to find that GluD1 binds GABA. “Its role in the brain is therefore not a priori exciter of neuronal activity but inhibitory”they insist. “When activated by the presence of GABA, the inhibitory synapse sees its effectiveness increase. This results in a greater inhibitory response that lasts for tens of minutes,” they add. Another discovery: GluD1 does not function as a receptor “classic”. Unlike the others, it does not allow the opening of any channel in the cell membrane. “Its activity results from other mechanisms internal to the cell which remain to be clarified,” say the scientists.
Excitators VS inhibitors: restoring imbalances
“These results open the way to a better understanding of the imbalances between excitatory and inhibitory messages in the brain in cases of TND or diseases such as epilepsy, characterized by neuronal hyper excitability,” they conclude. Next step: evaluate whether GluD1 can constitute a “interesting therapeutic target” in order to restore a better balance and reduce the symptoms in these disorders and pathologies.
* from the CNRS (National Center for Scientific Research) and the ENS within the Institute of Biology of the Ecole Normale Supérieure (IBENS, Paris) with the molecular biology laboratory of the MRC (Medical Research Council) of Cambridge (United Kingdom)
“All rights of reproduction and representation reserved.© Handicap.fr. This article was written by Cassandre Rogeret, journalist Handicap.fr”
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