HEALTH NEWS

Study Title:

How Cortiscol Helps You Adapt to Stress

Study Abstract

Corticosterone facilitates hippocampal glutamate transmission, but the cellular pathways by which AMPA receptor (AMPAR) signaling is adjusted remain elusive. Single quantum-dot imaging in live rat hippocampal neurons revealed that corticosterone triggers, via distinct corticosteroid receptors, time-dependent increases in GluR2-AMPAR surface mobility and synaptic surface GluR2 content. Furthermore, corticosterone potentiates the increase of synaptic surface GluR2 contents by a chemical long-term potentiation stimulus, revealing the influence that corticosterone has on AMPAR trafficking.

From press release:

Stress Hormone Found To Regulate Brain Neurotransmission

CNRS and Inserm(1) researchers, working at the future NeuroCampus in Bordeaux, have just shown how one of the stress hormones regulates brain neurotransmission on the short and long term and enables neuronal connections to adapt.

This work, directed by Laurent Groc and Francis Chaouloff, may lead to the identification of new therapeutic targets for psychiatric illnesses such as post-traumatic stress disorder and depression.

When we are subjected to a stress, our adrenal glands secrete hormones that affect our entire body. One of these hormones, cortisol, enables us to adapt physically and mentally to the stimulus. Following a major or repeated stress that the individual has no control over, however, cortisol is secreted in great quantities over a long period of time. This hypersecretion has damaging effects on the individual, to the point of accelerating aging and facilitating the onset of illnesses such as depression.

The researchers have shown that in one part of the brain, the hippocampus, corticosterone (the equivalent of human cortisol in laboratory rats) modifies the intensity of transmissions made by excitatory synapses(2). To the researchers' great surprise, this hormone increases the mobility of receptors found on the surface of neurons, thus allowing synaptic connections to adapt more effectively to the demands of brain activity. The stress hormone can be thought of as an alarm that mobilizes the receptors.

In addition, briefly exposing neurons to corticosterone increases synaptic plasticity(3), due to increased receptor mobility. Although this first effect is beneficial, in the case of prolonged stress (corticosterone stimulation over several hours), synaptic plasticity is reduced. This inverse effect can be explained by the fact that after a certain amount of time, the stress hormone not only increases receptor mobility, but also increases the number of receptors mobilized at the synapse level, leading to a decrease in plasticity.

The characterization of these newly discovered mechanisms opens up numerous possibilities for future research that could enhance both fundamental knowledge and clinical benefits. We can now imagine that in certain individuals subjected to major stress, lack of receptor mobility contributes to a lack of adaptation. Under stressful conditions, synaptic plasticity would then depend on the dynamic interactions between cortisol and the neuronal receptors that modulate brain activity. In the end, better mobility means better adaptation.

Notes:

(1) Laboratoire Physiologie Cellulaire de la Synapse UMR5091 CNRS and Neurocentre U862 Inserm, Université de Bordeaux.

(2) Excitatory synapses represent more than 80% of synapses. The neurons communicate between each other at the synapse level. Broadly, this junction contains a pre-synaptic element, which sends the information, and a post-synaptic element that receives the information. When the pre-synaptic compartment is stimulated by an electrical signal, it releases chemical messengers called neurotransmitters. Then, several milliseconds later, these neurotransmitters bind to special receptors.

(3) A synapse's ability to modify the information that it transmits.

Study Information

Groc L., Choquet D., Chaouloff F.
The stress hormone corticosterone conditions AMPA receptor surface trafficking and synaptic potentiation.
Nature Neuroscience
2008 July
Laboratoire Physiologie Cellulaire de la Synapse UMR5091 CNRS and Neurocentre U862 Inserm, Université de Bordeaux.