Neurotransmitter receptors in oligodendrocytes



GABAB receptors in oligodendrocytes for (re)myelination

Myelin formation in the central nervous system is driven by oligodendrocytes, which must differentiate from oligodendrocyte progenitor cells (OPCs) in order to perform their role. Gamma-aminobutiric acid (GABA) is an inhibitory neurotransmitter of the central nervous system that has been described as a relevant modulator of OPC differentiation and functions, as part of the regulation driven by neuron-OL communication. Adverse myelination or oligodendrocyte functionality has been linked to several pathologies such as Alzheimer’s Disease, schizophrenia or autism spectrum disorders (ASD), and remarkably, OPC differentiation impairment and myelin damage is critical in demyelinating diseases such as multiple sclerosis (MS). 

Given the potential to modulate oligodendrocyte plasticity through GABAergic signaling and particularly through GABAB receptors, our main research goals are:

With that aim, we make use of molecular and histological techniques, combining in vitro primary cultures, animal models of demyelinating diseases, transgenic mice and patient samples.

Funded by Ministerio de Ciencia e Innovación

Primary oligodendrocytes (cyan) in culture. Nuclei in magenta.

Role of oligodendrocyte NMDA receptors in autoimmune encephalitis

Antibodies against neuronal N-methyl-D-aspartate receptors (NMDARs) in patients with anti-NMDAR encephalitis alter neuronal synaptic function and plasticity, but the effects on other cells of the nervous system are unknown. By using cerebrospinal fluid from patients, full of anti-NMDARs antibodies, we have determined alterations in oligodendrocyte function. Antibodies from patients with anti-NMDAR encephalitis specifically alter the function of NMDARs in oligodendrocytes, causing a decrease of expression of GLUT1 and NMDA-dependent cytosolic calcium response. Considering that normal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal function, the findings suggest a link between antibody-mediated dysfunction of NMDARs in oligodendrocytes and the white matter alterations reported in patients with this disorder.

Funded by CIBERNED, Basque Government and Ministerio de Ciencia e Innovación

Patients' NMDA auto-antibodies reduce the expression of glucose-transporter 1, needed for proper metabolic function 

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