The chemokine BRAK/CXCL14 regulates synaptic transmission in the adult mouse dentate gyrus stem cell niche.

ABSTRACT

The chemokine BRAK/CXCL14 is an ancient member of the chemokine family whose functions in the brain are completely unknown. We examined the distribution of CXCL14 in the nervous system during development and in the adult. Generally speaking, CXCL14 was not expressed in the nervous system prior to birth, but it was expressed in the developing whisker follicles (E14.5) and subsequently in the hair follicles and skin. Postnatally, CXCL14 was also highly expressed in many regions of the brain, including the cortex, basal ganglia, septum and hippocampus. CXCL14 was also highly expressed in the dorsal root ganglia. We observed that in the hippocampal dentate gyrus (DG) CXCL14 was expressed by GABAergic interneurons. We demonstrated that CXCL14 inhibited GABAergic transmission to nestin-EGFP-expressing neural stem/progenitor cells in the adult DG. CXCL14 inhibited both the tonic and phasic effects of synaptically released GABA. In contrast CXCL12 enhanced the effects of GABA at these same synapses. CXCL14 increased [Ca(2+)](i) in neural stem cells cultured from the postnatal brain indicating that they expressed the CXCL14 receptor. These observations are consistent with the view that CXCL12 and CXCL14 may normally act as positive and negative regulators of the effects of GABA in the adult DG stem cell niche.