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Researchers Discover Key to Survival of Brain Cells
Receptors, called NMDARs, are located
both inside and outside of the synapses;
© panthermedia.net/Heike Brauer
These findings reveal how receptor signalling takes place between receptors of synapses (gaps between neurons through which chemical or electrical signals pass permitting cells to "talk" to each other) and the mechanisms involved in initiating disease. The receptors, called NMDARs, are located both inside and outside of the synapses. Activation of the NMDRs inside (synaptic) allows the synapse to adjust response to signals and activation of the synaptic NMDRs is also required for survival of the cell. In contrast, activation of the receptors outside the synapse (extra synaptic) leads to cell death.
The LSUHSC research team believed that activation of the extra synaptic NMDRs promotes the pathological effects of cyclooxygenase 2 (COX-2), a protein known to contribute to inflammation associated with neurotoxicity. They found that activating the synaptic NMDRs greatly increased levels of COX-2, but not of the chemical (arachidonic acid) upon which COX-2 acts. Conversely, activating the extra synaptic NMDRs increased the levels of arachidonic acid, but not COX-2. The researchers discovered, however, when synaptic and extra synaptic NMDARs were sequentially activated, the levels of both COX-2 and arachidonic acid increased, as did neurotoxic inflammation.
"We have discovered a fascinating relationship regarding the "conversations" that occur between these two receptors in the brain," said Bazan.
"We demonstrate how these signals affect cell functions and how they lead to diseases, including stroke, epilepsy and other neurodegenerative disorders. Targeting mechanisms that couple sequential synaptic then extra synaptic NMDAR stimulations may lead to new anti-inflammatory/neuroprotective approaches."
MEDICA.de; Source: Louisiana State University Health Sciences Centre