Sublamina‐specific organization of the blood brain barrier in the mouse olfactory nerve layer

Abstract

Astrocytes constitute the main glial component of the mammalian blood brain barrier (BBB). However, in the olfactory bulb (OB), the olfactory nerve layer (ONL) is almost devoid of astrocytes, raising the question which glial cells are part of the BBB. We used mice expressing EGFP in astrocytes and tdTomato in olfactory ensheathing cells (OECs), a specialized type of glial cells in the ONL, to unequivocally identify both glial cell types and investigate their contribution to the BBB in the olfactory bulb. OECs were located exclusively in the ONL, while somata of astrocytes were located in deeper layers and extended processes in the inner sublamina of the ONL. These processes surrounded blood vessels and contained aquaporin‐4, an astrocytic protein enriched at the BBB. In the outer sublamina of the ONL, in contrast, blood vessels were surrounded by aquaporin‐4‐negative processes of OECs. Transcardial perfusion of blood vessels with lanthanum and subsequent visualization by electron microscopy showed that blood vessels enwrapped by OECs possessed intact tight junctions. In acute olfactory bulb preparations, injection of fluorescent glucose 6‐NBDG into blood vessels resulted in labeling of OECs, indicating glucose transport from the perivascular space into OECs. In addition, Ca2+ transients in OECs in the outer sublamina evoked vasoconstriction, whereas Ca2+ signaling in OECs of the inner sublamina had no effect on adjacent blood vessels. Our results demonstrate that the BBB in the inner sublamina of the ONL contains astrocytes, while in the outer ONL OECs are part of the BBB.

Norepinephrine-Induced Calcium Signaling and Store-Operated Calcium Entry in Olfactory Bulb Astrocytes

“…Another gliotransmitter released by olfactory bulb astrocytes is ATP that is degraded to adenosine, a potent neuromodulator in the olfactory bulb (Roux et al, 2015;Schulz et al, 2017;Rotermund et al, 2018). Besides gliotransmission, astrocytes contribute to the blood brain barrier, mediate neurovascular coupling, and hence adjust local blood flow (Petzold et al, 2008;Doengi et al, 2009;Otsu et al, 2015;Beiersdorfer et al, 2020). Olfactory bulb astrocytes not only transmit information to neurons and blood vessels, but also to olfactory ensheathing cells, another type of glial cell that is coupled to astrocytes in a panglial network (Beiersdorfer et al, 2019).…”

Insights into olfactory ensheathing cell development from a laser‐microdissection and transcriptome‐profiling approach

“…Recently, the glia limitans was reported to be formed by astrocytes, just as elsewhere in the CNS, suggesting that all OECs are peripheral glia, including those within the olfactory nerve layer (ONL) of the olfactory bulb (Nazareth et al, 2019). However, juxtaglomerular OECs (in the innermost ONL) are coupled to astrocytes by gap junctions (Beiersdorfer, Scheller, Kirchhoff, & Lohr, 2019) and although astrocytes form the blood–brain barrier in the glomerular layer and the inner ONL, OECs in the outer ONL contribute to the blood–brain barrier (Beiersdorfer et al, 2020). Overall, OECs seem to exhibit properties of both CNS and peripheral glia and form part of the transitional zone between the peripheral and central nervous systems (Beiersdorfer et al, 2020).…”

Novel factor in olfactory ensheathing cell‐astrocyte crosstalk: Anti‐inflammatory protein α‐crystallin B

“…OECs are present along the entire route traversed by the olfactory sensory axons, that is, from the nasal cavity to the olfactory nerve layer in the olfactory bulb, where they can encounter CNS astrocytes (Li et al, 2005; Raisman & Li, 2007; Williams, Franklin, & Barnett, 2004). Communication between OECs and astrocytes in the OB can be regulated by both gap‐junctions and via transmission of extracellular factors (Beiersdorfer et al, 2020). Notably, both transplanted OECs (Lakatos et al, 2003; reviewed in Roet & Verhaagen, 2014) and co‐cultured OECs (Hale et al, 2011; Lakatos, Franklin, & Barnett, 2000) have been shown to intermingle with astrocytes and to moderate astrocyte activation.…”