Aims: 

Oligodendrocytes (OLs) are responsible for axon myelination and are the principle cells affected in preterm white matter injury (WMI). Our aims are to define the functional role ofMetabotropic glutamate receptors (mGluRs) and GABA_B receptors (GABA_BRs) in OL development and the mechanisms underlying OL survival and vulnerability in the developing brain.

Methods: 

Primary oligodendroglial cultures, acute brain slice preparations and in vivo rat model of WMI were used to define the role of GABA_BRs and mGluRs in OL development and viability.

Results: 

We have characterised the expression, signalling and functions of mGluRs (mGluR3 and mGluR5a isoforms) and GABA_BRs in developing OLs in both cultured cells and brain samples. While activation of mGluR5a limits apoptosis, GABA_BR activation stimulates proliferation and migration of OL progenitor cells in different experimental systems.

Conclusions: 

OL progenitor cells express functional mGluR3, mGluR5a and GABA_BRs in vitro and in situ. mGluRs and GABA_BRs in developing OLs provide a potentially important mechanism for neuronal-glial interactions in the immature brain. The down-regulation of mGluR5a in premyelinating OLs is likely to contribute to their increased vulnerability. These receptors may offer novel targets for white matter protection/regeneration. The GABA_BR agonist baclofen promotes OL progenitor cell proliferation and migration and therefore may be able to improve myelin regeneration following hypoxia-ischaemia-induced WMI.

Support: 

BBSRC (grant BB/F011326/1)