Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: A confocal microscopy study

Abstract

Despite the increasing evidence for a prominent role played by the perivascular endfeet of astrocytes in the functional metabolic coupling between astrocytes and neurons, a clear picture of their spatial organization is still lacking. To examine the three-dimensional structure of the astrocyte endfeet and their relationships with the endothelial cells, coronal rat brain sections immunolabeled for the two astroglial markers [glial fibrillary acidic protein (GFAP)/S-100beta] and the endothelial glucose transporter (GLUT1) were analyzed under the confocal microscope. Double immunolabeling of GFAP and S-100beta showed numerous well-defined astrocytes sending one or more endfeet to the vasculature. Examination of GFAP immunolabeling at higher magnification showed that these endfeet consist of well-defined rosette-like structures lying on the vessel wall. Double immunostaining of GFAP and GLUT1 showed that the endothelial cells were the main targets of these repeated geometrical units formed by the astrocyte endfeet. When three-dimensional images were reconstructed, obvious privileged anatomical relationships were observed between endfeet and individual endothelial cells. These anatomical data provide strong support for the involvement of astrocytes in cerebral metabolic coupling. The finger-like appearance of astrocyte endfeet could allow direct metabolic exchanges between intracerebral vessels and non-glial elements such as nerve terminals.

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

“…In presymptomatic SOD1 G93A mice, immune activation in the peripheral and central nervous system begins focally and becomes widespread after clinical onset (Alexianu, Kozovska, & Appel, 2001; Chiu et al, 2009; Hall, Oostveen, & Gurney, 1998). Macrophage activation in the peripheral nervous system occurs in parallel with microglial activation and T‐cell infiltration in the spinal cord (Chiu et al, 2009).…”

Immunolocalization of tight junction proteins in the adult and developing human brain

“…The possible candidates for this signaling role are envelopes of perivascular astrocytes and astrocyte endfeet forming the glial limiting membrane underlying the leptomeningeal sheet. Several studies have shown that astrocytes participate in the induction of barrier properties in endothelial cells by direct contact and/or releasing of soluble factors (Janzer and Raff 1987;Laterra et al 1990;Cassella et al 1996;Kacem et al 1998;Pekny et al 1998;Sobue et al 1999;Abbott 2002;Willis et al 2004). In human fetal telencephalon, radial glia cells make contacts with the walls of telencephalon microvessels and terminate by forming the glial limiting membrane at the leptomeningeal surface (Marín-Padilla 1995;Virgintino et al 1998b;Bertossi et al 1999).…”

Dynamics of CNS Barriers: Evolution, Differentiation, and Modulation

“…The heavy arrows indicate the ability of the endothelium to release agents to the blood or brain side following receptor activation, as part of their 'effector' function. a meshwork on the outer surface and share a basal lamina with the endothelium (Allt and Lawrenson, 2001), and the end-feet of perivascular astrocytes form a further covering of fine processes and lamellae punctuated by gaps (Kacem et al, 1998). Neuronal terminals, microglia and other 'perivascular cells' are found in the perivascular space, and smooth muscle layers, in some cases together with sheaths derived from the meninges, are present in arterioles, arteries and larger veins (Weller et al, 1992).…”

“…Three-dimensional visualization of the microanatomy of glial-endothelial interaction in brain sections suggests some 'microdomains' of influence, with single endothelia associated with single astrocytes (Kacem et al, 1998). Culture studies show that the induction is more effective when the target endothelium is derived from brain microvessels (Dehouck et al, 1990;Reinhart and Gloor, 1997), suggesting that even when cultured, the brain endothelium 'remembers' aspects of its original phenotype-now increasingly demonstrated at the molecular level from examination of gene and protein expression in these cells (Li et al, 2001;Desai et al, 2002).…”