ABCA2 is a marker of neural progenitors and neuronal subsets in the adult rodent brain

Abstract

The notion that the ATP-binding cassette transporter-A2 (ABCA2) may be involved in brain sterol homeostasis and is associated with early onset Alzheimer's disease led us to explore its neural expression. Our data support and extend the previous reports on ABCA2 expression by oligodendrocytes. They evidence that ABCA2 (i) is located in intracellular vesicles, identified in transfected cells as lysosome-related organelles only partially overlapping with classical endolysosomes; (ii) is a marker of neural progenitors as it is expressed in the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampal formation, sites of continual neurogenesis in the adult brain, and in nestin + cells differentiated in vitro from embryonic stem cells; (iii) persists, in the adult rodent brain, in a subset of GABAergic and glutamatergic neurons. Considering that the latter are targets of Alzheimer's lesions, these data provide a new rationale to explore the neuropathological consequences of ABCA2 functional dysregulations.

ABC transporters, neural stem cells and neurogenesis – a different perspective

“…Chiba et al [131] suggested that ABCB1 rather than ABCG2 is involved in their "PLC/PRF/5" SP cell phenotype . The published studies on NSCs support the hypothesis that ABCB1 (MDR1) might be more important than ABCG2 in controlling the specific phenotype of NSCs [166][167][168], in contrast to the HSCs where ABCG2 is involved in the SP phenotype and considered as its molecular determinant. In short, ABC transporters have emerged as an important new field of investigation in the regulation of stem cell biology, and manipulation of this system may promote stem cell amplification via a common defence mechanism adopted by these cells through their high expression of ABC membrane transporters [170].…”

“…Recent results show that NSCs from mouse forebrain are contained in a population distinct from the SP [134]. Moreover, other research data show that the ABCA2 transporter is widely expressed in early neural progenitors developed in vitro from ES cells [166]. ABCA2 expression in the adult mouse and rat brains seems to be region-dependent because it is limited to the oligodendrocytic lineage -unambiguously excluded from astrocytes -and to a subset of cortical GABAergic inter-neurons and pyramidal glutamatergic neurons where it could be localized to lysosomal-related organelles [166].…”

“…ABCA2 expression in the adult mouse and rat brains seems to be region-dependent because it is limited to the oligodendrocytic lineage -unambiguously excluded from astrocytes -and to a subset of cortical GABAergic inter-neurons and pyramidal glutamatergic neurons where it could be localized to lysosomal-related organelles [166]. ABCA2 has also been suggested to be a marker of neural progenitors as it is expressed in the subventricular zone of the lateral ventricle and the DG of the hippocampal formation, sites of continual neurogenesis in the adult brain, and in nestin+ cells differentiated in vitro from ES cells [166].…”

“…npg inhibitor (cyclosporine A) at a very low dose, suggested that the ABC transporter may contribute to neural stem/ progenitor cell expansion [167,168]. While ABCA2 shows higher expression in nestin+ mouse neural progenitors, at later developmental stages it undergoes a conspicuous downregulation, persisting only in limited subsets of differentiated neurons [166]. Based on these results and the observations that the ABC transporters are expressed at high levels in hNSPCs but are downregulated in differentiated hNSPCs (Figure 3), we hypothesize that these genes could potentially function as putative NSC markers in a similar way as p21CIP/WAF or musashi-1.…”

Abca7 deletion does not affect adult neurogenesis in the mouse

“…Our rationale for asking this question is based on previous studies showing that other ABC transporters including two that, like ABCA7, are also from the "Class-A" subfamily (i.e. ABCA2, ABCA3) appear to play a role in neurogenesis [15,16]. These studies along with the extensive literature highlighting the importance of adult neurogenesis in AD (see [17][18][19][20], for recent comprehensive reviews of this area) prompted our present study in which we have assessed cellular proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ) of both WT and Abca7 − / − adult male mice.…”