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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Journal of Translational Medicine 1/2014

Existence of a potential neurogenic system in the adult human brain

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2014
Autoren:
Adriano Barreto Nogueira, Mari Cleide Sogayar, Alison Colquhoun, Sheila Aparecida Siqueira, Ariel Barreto Nogueira, Paulo Eurípedes Marchiori, Manoel Jacobsen Teixeira
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1479-5876-12-75) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

ABN (first author): wrote the grant applications; contributed materials and analysis tools; conceived, designed and carried out the experiments; analyzed and interpreted the data; wrote the paper. MCS: participated in coordination; wrote the grant applications; contributed materials and analysis tools; revised the manuscript. AC: contributed materials and analysis tools; designed and carried out the experiments; analyzed and interpreted the data; revised the manuscript. SAS: contributed materials and analysis tools; analyzed the data; revised the manuscript. ABN (co-author): designed and carried out experiments; analyzed the data; revised the manuscript. RS: contributed materials; analyzed the data; revised the manuscript. PEM: participated in coordination; revised the manuscript. MJT: participated in coordination; wrote the grant applications; revised the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Prevailingly, adult mammalian neurogenesis is thought to occur in discrete, separate locations known as neurogenic niches that are best characterized in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). The existence of adult human neurogenic niches is controversial.

Methods

The existence of neurogenic niches was investigated with neurogenesis marker immunostaining in histologically normal human brains obtained from autopsies. Twenty-eight adult temporal lobes, specimens from limbic structures and the hypothalamus of one newborn and one adult were examined.

Results

The neural stem cell marker nestin stained circumventricular organ cells and the immature neuronal marker doublecortin (DCX) stained hypothalamic and limbic structures adjacent to circumventricular organs; both markers stained a continuous structure running from the hypothalamus to the hippocampus. The cell proliferation marker Ki-67 was detected predominately in structures that form the septo-hypothalamic continuum. Nestin-expressing cells were located in the fimbria-fornix at the insertion of the choroid plexus; ependymal cells in this structure expressed the putative neural stem cell marker CD133. From the choroidal fissure in the temporal lobe, a nestin-positive cell layer spread throughout the SVZ and subpial zone. In the subpial zone, a branch of this layer reached the hippocampal sulcus and ended in the SGZ (principally in the newborn) and in the subiculum (principally in the adults). Another branch of the nestin-positive cell layer in the subpial zone returned to the optic chiasm. DCX staining was detected in the periventricular and middle hypothalamus and more densely from the mammillary body to the subiculum through the fimbria-fornix, thus running through the principal neuronal pathway from the hippocampus to the hypothalamus. The column of the fornix forms part of this pathway and appears to coincide with the zone previously identified as the human rostral migratory stream. Partial co-labeling with DCX and the neuronal marker βIII-tubulin was also observed.

Conclusions

Collectively, these findings suggest the existence of an adult human neurogenic system that rises from the circumventricular organs and follows, at minimum, the circuitry of the hypothalamus and limbic system.
Zusatzmaterial
Additional file 4: Figure S1: PCNA staining of oligodendrocytes in the fornix depicts a pattern corresponding to a cell cluster stream. The immunohistochemical results obtained with a polymeric detection system are more sensitive than those obtained with other commonly used immunohistochemical methods. With the polymeric detection system, most of the nuclei are stained for PCNA, except neuronal nuclei (arrows in (D) and (E) show hematoxylin-stained nuclei of granule cells and pyramidal neurons, respectively). Moreover, staining of structures such as astrocyte cytoplasm (arrowheads in (D) and (E)) is most likely a result of polymer leakage from the nucleus. Oligodendrocytes appear as lined clusters in the white matter and stains for PCNA (arrows in (B)), forming a pattern in the fornix (f) (upper arrow in (B)) that may misinterpreted as immature neural cells in the human counterpart of the RMS. (A), parasagittal section at the antero-inferior boundary of the foramen of Monro (fm) zone; (B), magnified view of box B depicted in (A); (C), coronal section of the hippocampal formation encompassing the granule cell layer (gcl) of the dentate gyrus and the hippocampus proper; (D) and (E) are magnified views of the corresponding boxes depicted in (C). (e), ependymal cell layer (note that this layer penetrates into the parenchyma similar to the intraparenchymal ependymal layer in the hippocampus); (ml), molecular layer; (th), thalamus; (tsz), thalamic stratum zonale. Scale bars: (A) = 200 μm; (B) and (E) = 100 μm; (C) = 500 μm; (D) = 50 μm. (TIFF 6 MB)
Additional file 5: Figure S2: Vimentin staining. Vimentin is a putative NSC marker. In the SVZ (A) and (B), vimentin stains the ependymal layer and the anuclear gap (left side of the image) and NSCs (arrow in (B)). The pattern of vimentin staining in the body of the hippocampus (C) and in the SGZ (D) is similar to the pattern of nestin staining in these regions. Note the larger layer of vimentin-positive cells in the fimbriodentate sulcus (arrow in (C)) and the darker color in the fimbria (letter F in (C)) compared to the remaining parenchyma (see also Figure 5). Nonetheless, vimentin is a less specific NSC marker than nestin because it also stains protoplasmic astrocytes (arrows in (E) (amygdala) and in (F) (neocortex)). GCL, granule cell layer; H, hilus; ML, molecular layer. Arrow in (D), nestin positive process in the GCL from a NPC located in the SGZ. Arrowhead in (F), endothelium stained by vimentin. Scale bars: 50 μm. (TIFF 4 MB)
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