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FP7

CeLEStIaL Result In Brief

Project ID: 302939
Funded under: FP7-PEOPLE
Country: Switzerland

The molecular basis of nervous system communication

Smooth nervous system functioning depends on continuous interactions among its different components, mainly neurons and glial cells. Comprehending their communication mechanism is central for restoring neuronal dysfunction in neuropathies.
The molecular basis of nervous system communication
Glial cells are vital for producing myelin, which insulates neurons, providing trophic support and participating in immune responses. Perturbation of neuron-glia communication occurs during injury, in acquired or hereditary neurological disorders, and with ageing. However, the specific nature and the physiological significance of neuron-glia interactions remain largely unknown.

The EU-funded CELESTIAL (Identification of molecular pathways underlying activity-dependent neuron-glia communication using in vitro microfluidic systems) project proposed to investigate the molecular mechanisms mediating these cell interactions. The long-term plan was to develop novel and more efficient therapeutic interventions for diseases where the physiological neuron-glia interaction is compromised.

Considering that neurons consist of three main parts (cell body, the neuronal processes and synapses), glial cells can interact with any of these parts. The work of CELESTIAL focused on the interaction of glial cells with neurites, known as 'extrasynaptic' communication in the peripheral nervous system.

Scientists developed a microfluidic co-culture platform to characterise and investigate the role of non-synaptic responses of glial cells following stimulation of neuronal activity. This cell culture system has dual compartments for the separation of neuronal cell bodies from neurites and Schwann cells. Subsequent electrical stimulation of the different neuronal parts allowed researchers to study signal transmission, cellular reactions to neuronal signals as well as mitochondrial behaviour.

In addition, project researchers examined the release of neurotransmitters after electrical stimulation and their role in Schwann cell physiology. Coupled with in vivo data, results pointed towards a specific neuropeptide transmitter capable of modulating communication between neurons and Schwann cells. Further work in animal models led to the identification of a promising candidate gene that is upregulated in Schwann cells during neuropathy, possibly contributing to the observed compromised neuronal activity.

Collectively the CELESTIAL work provides fundamental insight into the mechanisms underlying the interaction between neurons and glial cells. Importantly, it opens up pathways for manipulating the particular signalling pathway as a therapeutic intervention in people suffering from inherited peripheral neuropathies.

Related information

Keywords

Nervous system, neuron, glial cells, Schwann cells, neurotransmitters
Record Number: 175180 / Last updated on: 2016-02-19
Domain: Biology, Medicine
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